|
Inhibition of TPA-induced Epstein-Barr virus early antigen activation in Raji cells at 1000 mol ratio/32 pmol TPA relative to control
|
Human herpesvirus 4
|
8.6
%
|
|
Journal : J. Nat. Prod.
Title : Triterpene acids from Poria cocos and their anti-tumor-promoting effects.
Year : 2007
Volume : 70
Issue : 6
First Page : 948
Last Page : 953
Authors : Akihisa T, Nakamura Y, Tokuda H, Uchiyama E, Suzuki T, Kimura Y, Uchikura K, Nishino H.
Abstract : The structures of six new lanostane-type triterpene acids isolated from the epidermis of the sclerotia of Poria cocos were established to be 15alpha-hydroxydehydrotumulosic acid (5), 16alpha,25-dihydroxydehydroeburicoic acid (9), 5alpha,8alpha-peroxydehydrotumulosic acid (10), 25-hydroxyporicoic acid H (11), 16-deoxyporicoic acid B (12), and poricoic acid CM (16) on the basis of spectroscopic methods. On evaluation of these six and 11 other known triterpene acids isolated from the sclerotium, 1-4, 6-8, 13-15, and 17, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds except for 1, 3, 4, and 8 exhibited inhibitory effects with IC50 values of 195-340 mol ratio/32 pmol TPA. Compound 12 and poricoic acid C (13) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen activation in Raji cells at 500 mol ratio/32 pmol TPA relative to control
|
Human herpesvirus 4
|
34.2
%
|
|
Journal : J. Nat. Prod.
Title : Triterpene acids from Poria cocos and their anti-tumor-promoting effects.
Year : 2007
Volume : 70
Issue : 6
First Page : 948
Last Page : 953
Authors : Akihisa T, Nakamura Y, Tokuda H, Uchiyama E, Suzuki T, Kimura Y, Uchikura K, Nishino H.
Abstract : The structures of six new lanostane-type triterpene acids isolated from the epidermis of the sclerotia of Poria cocos were established to be 15alpha-hydroxydehydrotumulosic acid (5), 16alpha,25-dihydroxydehydroeburicoic acid (9), 5alpha,8alpha-peroxydehydrotumulosic acid (10), 25-hydroxyporicoic acid H (11), 16-deoxyporicoic acid B (12), and poricoic acid CM (16) on the basis of spectroscopic methods. On evaluation of these six and 11 other known triterpene acids isolated from the sclerotium, 1-4, 6-8, 13-15, and 17, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds except for 1, 3, 4, and 8 exhibited inhibitory effects with IC50 values of 195-340 mol ratio/32 pmol TPA. Compound 12 and poricoic acid C (13) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen activation in Raji cells at 100 mol ratio/32 pmol TPA relative to control
|
Human herpesvirus 4
|
82.1
%
|
|
Journal : J. Nat. Prod.
Title : Triterpene acids from Poria cocos and their anti-tumor-promoting effects.
Year : 2007
Volume : 70
Issue : 6
First Page : 948
Last Page : 953
Authors : Akihisa T, Nakamura Y, Tokuda H, Uchiyama E, Suzuki T, Kimura Y, Uchikura K, Nishino H.
Abstract : The structures of six new lanostane-type triterpene acids isolated from the epidermis of the sclerotia of Poria cocos were established to be 15alpha-hydroxydehydrotumulosic acid (5), 16alpha,25-dihydroxydehydroeburicoic acid (9), 5alpha,8alpha-peroxydehydrotumulosic acid (10), 25-hydroxyporicoic acid H (11), 16-deoxyporicoic acid B (12), and poricoic acid CM (16) on the basis of spectroscopic methods. On evaluation of these six and 11 other known triterpene acids isolated from the sclerotium, 1-4, 6-8, 13-15, and 17, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds except for 1, 3, 4, and 8 exhibited inhibitory effects with IC50 values of 195-340 mol ratio/32 pmol TPA. Compound 12 and poricoic acid C (13) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen activation in Raji cells at 10 mol ratio/32 pmol TPA relative to control
|
Human herpesvirus 4
|
100.0
%
|
|
Journal : J. Nat. Prod.
Title : Triterpene acids from Poria cocos and their anti-tumor-promoting effects.
Year : 2007
Volume : 70
Issue : 6
First Page : 948
Last Page : 953
Authors : Akihisa T, Nakamura Y, Tokuda H, Uchiyama E, Suzuki T, Kimura Y, Uchikura K, Nishino H.
Abstract : The structures of six new lanostane-type triterpene acids isolated from the epidermis of the sclerotia of Poria cocos were established to be 15alpha-hydroxydehydrotumulosic acid (5), 16alpha,25-dihydroxydehydroeburicoic acid (9), 5alpha,8alpha-peroxydehydrotumulosic acid (10), 25-hydroxyporicoic acid H (11), 16-deoxyporicoic acid B (12), and poricoic acid CM (16) on the basis of spectroscopic methods. On evaluation of these six and 11 other known triterpene acids isolated from the sclerotium, 1-4, 6-8, 13-15, and 17, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds except for 1, 3, 4, and 8 exhibited inhibitory effects with IC50 values of 195-340 mol ratio/32 pmol TPA. Compound 12 and poricoic acid C (13) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen activation assessed as EBV-EA induction in Raji cells at 320 nM after 48 hrs relative to TPA
|
Human herpesvirus 4
|
8.6
%
|
|
Journal : J. Nat. Prod.
Title : Cancer chemopreventive effects of cycloartane-type and related triterpenoids in in vitro and in vivo models.
Year : 2007
Volume : 70
Issue : 6
First Page : 918
Last Page : 922
Authors : Kikuchi T, Akihisa T, Tokuda H, Ukiya M, Watanabe K, Nishino H.
Abstract : Forty-eight natural and semisynthetic cycloartane-type and related triterpenoids have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for anti-tumor promoters. In addition, these triterpenoids have been tested for their inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All of the compounds tested exhibited inhibitory effects on both EBV-EA and NOR 1 activation. Six of these compounds having a C-24 hydroxylated side chain, viz., (24R)-cycloart-25-ene-3beta,24-diol (9), (24R)-cycloartane-3beta,24,25-triol (11), (24S)-cycloartane-3beta,24,25-triol (12), (24xi)-24-methylcycloartane-3beta,24,241-triol (14), (24xi)-241-methoxy-24-methylcycloartane-3beta,24-diol (15), and (24xi)-24,25-dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others tested on both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation. Furthermore, compounds 14 and 15 exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen activation assessed as EBV-EA induction in Raji cells at 32 nM after 48 hrs relative to TPA
|
Human herpesvirus 4
|
34.2
%
|
|
Journal : J. Nat. Prod.
Title : Cancer chemopreventive effects of cycloartane-type and related triterpenoids in in vitro and in vivo models.
Year : 2007
Volume : 70
Issue : 6
First Page : 918
Last Page : 922
Authors : Kikuchi T, Akihisa T, Tokuda H, Ukiya M, Watanabe K, Nishino H.
Abstract : Forty-eight natural and semisynthetic cycloartane-type and related triterpenoids have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for anti-tumor promoters. In addition, these triterpenoids have been tested for their inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All of the compounds tested exhibited inhibitory effects on both EBV-EA and NOR 1 activation. Six of these compounds having a C-24 hydroxylated side chain, viz., (24R)-cycloart-25-ene-3beta,24-diol (9), (24R)-cycloartane-3beta,24,25-triol (11), (24S)-cycloartane-3beta,24,25-triol (12), (24xi)-24-methylcycloartane-3beta,24,241-triol (14), (24xi)-241-methoxy-24-methylcycloartane-3beta,24-diol (15), and (24xi)-24,25-dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others tested on both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation. Furthermore, compounds 14 and 15 exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen activation assessed as EBV-EA induction in Raji cells at 3.2 nM after 48 hrs relative to TPA
|
Human herpesvirus 4
|
82.1
%
|
|
Journal : J. Nat. Prod.
Title : Cancer chemopreventive effects of cycloartane-type and related triterpenoids in in vitro and in vivo models.
Year : 2007
Volume : 70
Issue : 6
First Page : 918
Last Page : 922
Authors : Kikuchi T, Akihisa T, Tokuda H, Ukiya M, Watanabe K, Nishino H.
Abstract : Forty-eight natural and semisynthetic cycloartane-type and related triterpenoids have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for anti-tumor promoters. In addition, these triterpenoids have been tested for their inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All of the compounds tested exhibited inhibitory effects on both EBV-EA and NOR 1 activation. Six of these compounds having a C-24 hydroxylated side chain, viz., (24R)-cycloart-25-ene-3beta,24-diol (9), (24R)-cycloartane-3beta,24,25-triol (11), (24S)-cycloartane-3beta,24,25-triol (12), (24xi)-24-methylcycloartane-3beta,24,241-triol (14), (24xi)-241-methoxy-24-methylcycloartane-3beta,24-diol (15), and (24xi)-24,25-dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others tested on both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation. Furthermore, compounds 14 and 15 exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen activation assessed as EBV-EA induction in Raji cells at 0.32 nM after 48 hrs relative to TPA
|
Human herpesvirus 4
|
100.0
%
|
|
Journal : J. Nat. Prod.
Title : Cancer chemopreventive effects of cycloartane-type and related triterpenoids in in vitro and in vivo models.
Year : 2007
Volume : 70
Issue : 6
First Page : 918
Last Page : 922
Authors : Kikuchi T, Akihisa T, Tokuda H, Ukiya M, Watanabe K, Nishino H.
Abstract : Forty-eight natural and semisynthetic cycloartane-type and related triterpenoids have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for anti-tumor promoters. In addition, these triterpenoids have been tested for their inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All of the compounds tested exhibited inhibitory effects on both EBV-EA and NOR 1 activation. Six of these compounds having a C-24 hydroxylated side chain, viz., (24R)-cycloart-25-ene-3beta,24-diol (9), (24R)-cycloartane-3beta,24,25-triol (11), (24S)-cycloartane-3beta,24,25-triol (12), (24xi)-24-methylcycloartane-3beta,24,241-triol (14), (24xi)-241-methoxy-24-methylcycloartane-3beta,24-diol (15), and (24xi)-24,25-dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others tested on both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation. Furthermore, compounds 14 and 15 exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen activation in Raji cells after 48 hrs
|
Human herpesvirus 4
|
12.7
nM
|
|
Journal : J. Nat. Prod.
Title : Cancer chemopreventive effects of cycloartane-type and related triterpenoids in in vitro and in vivo models.
Year : 2007
Volume : 70
Issue : 6
First Page : 918
Last Page : 922
Authors : Kikuchi T, Akihisa T, Tokuda H, Ukiya M, Watanabe K, Nishino H.
Abstract : Forty-eight natural and semisynthetic cycloartane-type and related triterpenoids have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for anti-tumor promoters. In addition, these triterpenoids have been tested for their inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All of the compounds tested exhibited inhibitory effects on both EBV-EA and NOR 1 activation. Six of these compounds having a C-24 hydroxylated side chain, viz., (24R)-cycloart-25-ene-3beta,24-diol (9), (24R)-cycloartane-3beta,24,25-triol (11), (24S)-cycloartane-3beta,24,25-triol (12), (24xi)-24-methylcycloartane-3beta,24,241-triol (14), (24xi)-241-methoxy-24-methylcycloartane-3beta,24-diol (15), and (24xi)-24,25-dihydroxycycloartan-3-one (27), showed higher inhibitory effects than the others tested on both EBV-EA (IC50 values of 6.1-7.4 nM) and NOR 1 activation. Furthermore, compounds 14 and 15 exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen in Raji cells at 1000 mol ratio/TPA relative to control
|
Human herpesvirus 4
|
8.6
%
|
|
Journal : J. Nat. Prod.
Title : Cucurbitane-type triterpenoids from the fruits of Momordica charantia and their cancer chemopreventive effects.
Year : 2007
Volume : 70
Issue : 8
First Page : 1233
Last Page : 1239
Authors : Akihisa T, Higo N, Tokuda H, Ukiya M, Akazawa H, Tochigi Y, Kimura Y, Suzuki T, Nishino H.
Abstract : Thirteen cucurbitane-type triterpene glycosides, including eight new compounds named charantosides I (6), II (7), III (10), IV (11), V (12), VI (13), VII (16), and VIII (17), and five known compounds, 8, 9, 14, 15, and 18, were isolated from a methanol extract of the fruits of Japanese Momordica charantia. The structures of the new compounds were determined on the basis of spectroscopic methods. On evaluation of these triterpene glycosides and five other cucurbitane-type triterpenes, 1-5, also isolated from the extract of M. charantia fruits, for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, these compounds showed inhibitory effects on EBV-EA induction with IC(50) values of 200-409 mol ratio/32 pmol TPA. In addition, upon evaluation of compounds 1-5 for inhibitory effects against activation of (+/-)-(E)-methyl-2[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitrogen oxide (NO) donor, compounds 1-3 showed moderate inhibitory effects. Compounds 1 and 2 exhibited marked inhibitory effects in both 7,12-dimethylbenz[a]anthracene (DMBA)- and peroxynitrite (ONOO-; PN)-induced mouse skin carcinogenesis tests.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen in Raji cells at 500 mol ratio/TPA relative to control
|
Human herpesvirus 4
|
34.2
%
|
|
Journal : J. Nat. Prod.
Title : Cucurbitane-type triterpenoids from the fruits of Momordica charantia and their cancer chemopreventive effects.
Year : 2007
Volume : 70
Issue : 8
First Page : 1233
Last Page : 1239
Authors : Akihisa T, Higo N, Tokuda H, Ukiya M, Akazawa H, Tochigi Y, Kimura Y, Suzuki T, Nishino H.
Abstract : Thirteen cucurbitane-type triterpene glycosides, including eight new compounds named charantosides I (6), II (7), III (10), IV (11), V (12), VI (13), VII (16), and VIII (17), and five known compounds, 8, 9, 14, 15, and 18, were isolated from a methanol extract of the fruits of Japanese Momordica charantia. The structures of the new compounds were determined on the basis of spectroscopic methods. On evaluation of these triterpene glycosides and five other cucurbitane-type triterpenes, 1-5, also isolated from the extract of M. charantia fruits, for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, these compounds showed inhibitory effects on EBV-EA induction with IC(50) values of 200-409 mol ratio/32 pmol TPA. In addition, upon evaluation of compounds 1-5 for inhibitory effects against activation of (+/-)-(E)-methyl-2[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitrogen oxide (NO) donor, compounds 1-3 showed moderate inhibitory effects. Compounds 1 and 2 exhibited marked inhibitory effects in both 7,12-dimethylbenz[a]anthracene (DMBA)- and peroxynitrite (ONOO-; PN)-induced mouse skin carcinogenesis tests.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen in Raji cells at 100 mol ratio/TPA relative to control
|
Human herpesvirus 4
|
82.1
%
|
|
Journal : J. Nat. Prod.
Title : Cucurbitane-type triterpenoids from the fruits of Momordica charantia and their cancer chemopreventive effects.
Year : 2007
Volume : 70
Issue : 8
First Page : 1233
Last Page : 1239
Authors : Akihisa T, Higo N, Tokuda H, Ukiya M, Akazawa H, Tochigi Y, Kimura Y, Suzuki T, Nishino H.
Abstract : Thirteen cucurbitane-type triterpene glycosides, including eight new compounds named charantosides I (6), II (7), III (10), IV (11), V (12), VI (13), VII (16), and VIII (17), and five known compounds, 8, 9, 14, 15, and 18, were isolated from a methanol extract of the fruits of Japanese Momordica charantia. The structures of the new compounds were determined on the basis of spectroscopic methods. On evaluation of these triterpene glycosides and five other cucurbitane-type triterpenes, 1-5, also isolated from the extract of M. charantia fruits, for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, these compounds showed inhibitory effects on EBV-EA induction with IC(50) values of 200-409 mol ratio/32 pmol TPA. In addition, upon evaluation of compounds 1-5 for inhibitory effects against activation of (+/-)-(E)-methyl-2[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitrogen oxide (NO) donor, compounds 1-3 showed moderate inhibitory effects. Compounds 1 and 2 exhibited marked inhibitory effects in both 7,12-dimethylbenz[a]anthracene (DMBA)- and peroxynitrite (ONOO-; PN)-induced mouse skin carcinogenesis tests.
|
Inhibition of TPA-induced Epstein-Barr virus early antigen in Raji cells at 10 mol ratio/TPA relative to control
|
Human herpesvirus 4
|
100.0
%
|
|
Journal : J. Nat. Prod.
Title : Cucurbitane-type triterpenoids from the fruits of Momordica charantia and their cancer chemopreventive effects.
Year : 2007
Volume : 70
Issue : 8
First Page : 1233
Last Page : 1239
Authors : Akihisa T, Higo N, Tokuda H, Ukiya M, Akazawa H, Tochigi Y, Kimura Y, Suzuki T, Nishino H.
Abstract : Thirteen cucurbitane-type triterpene glycosides, including eight new compounds named charantosides I (6), II (7), III (10), IV (11), V (12), VI (13), VII (16), and VIII (17), and five known compounds, 8, 9, 14, 15, and 18, were isolated from a methanol extract of the fruits of Japanese Momordica charantia. The structures of the new compounds were determined on the basis of spectroscopic methods. On evaluation of these triterpene glycosides and five other cucurbitane-type triterpenes, 1-5, also isolated from the extract of M. charantia fruits, for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, these compounds showed inhibitory effects on EBV-EA induction with IC(50) values of 200-409 mol ratio/32 pmol TPA. In addition, upon evaluation of compounds 1-5 for inhibitory effects against activation of (+/-)-(E)-methyl-2[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitrogen oxide (NO) donor, compounds 1-3 showed moderate inhibitory effects. Compounds 1 and 2 exhibited marked inhibitory effects in both 7,12-dimethylbenz[a]anthracene (DMBA)- and peroxynitrite (ONOO-; PN)-induced mouse skin carcinogenesis tests.
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells at 1000 molar ratio after 48 hrs relative to TPA
|
Human herpesvirus 4
|
8.6
%
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory and anti-tumor-promoting effects of cucurbitane glycosides from the roots of Bryonia dioica.
Year : 2002
Volume : 65
Issue : 2
First Page : 179
Last Page : 183
Authors : Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Toriumi M, Koike K, Kimura Y, Nikaido T, Aoi W, Nishino H, Takido M.
Abstract : Seven new triterpene glycosides, bryoniosides A-G (1-7), have been isolated along with two known triterpene glycosides, cabenoside D (8) and bryoamaride (9), from a methanol extract of the roots of Bryoniadioica. The structures of 1-7 were determined on the basis of spectroscopic and chemical methods. Six compounds, 2, 3, 5, and 7-9, and 11 compounds, 1-9, bryodulcosigenin (10), and bryosigenin (11), respectively, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice and on Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA. All compounds tested showed marked anti-inflammatory effects, with 50% inhibitory doses (ID(50)) of 0.2-0.6 mg per ear. In addition, all of the compounds tested except for compound 5 showed potent inhibitory effects on EBV-EA induction (100% inhibition at 1 x 10(3) mol ratio/TPA).
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells at 500 molar ratio after 48 hrs relative to TPA
|
Human herpesvirus 4
|
34.2
%
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory and anti-tumor-promoting effects of cucurbitane glycosides from the roots of Bryonia dioica.
Year : 2002
Volume : 65
Issue : 2
First Page : 179
Last Page : 183
Authors : Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Toriumi M, Koike K, Kimura Y, Nikaido T, Aoi W, Nishino H, Takido M.
Abstract : Seven new triterpene glycosides, bryoniosides A-G (1-7), have been isolated along with two known triterpene glycosides, cabenoside D (8) and bryoamaride (9), from a methanol extract of the roots of Bryoniadioica. The structures of 1-7 were determined on the basis of spectroscopic and chemical methods. Six compounds, 2, 3, 5, and 7-9, and 11 compounds, 1-9, bryodulcosigenin (10), and bryosigenin (11), respectively, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice and on Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA. All compounds tested showed marked anti-inflammatory effects, with 50% inhibitory doses (ID(50)) of 0.2-0.6 mg per ear. In addition, all of the compounds tested except for compound 5 showed potent inhibitory effects on EBV-EA induction (100% inhibition at 1 x 10(3) mol ratio/TPA).
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells at 100 molar ratio after 48 hrs relative to TPA
|
Human herpesvirus 4
|
82.1
%
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory and anti-tumor-promoting effects of cucurbitane glycosides from the roots of Bryonia dioica.
Year : 2002
Volume : 65
Issue : 2
First Page : 179
Last Page : 183
Authors : Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Toriumi M, Koike K, Kimura Y, Nikaido T, Aoi W, Nishino H, Takido M.
Abstract : Seven new triterpene glycosides, bryoniosides A-G (1-7), have been isolated along with two known triterpene glycosides, cabenoside D (8) and bryoamaride (9), from a methanol extract of the roots of Bryoniadioica. The structures of 1-7 were determined on the basis of spectroscopic and chemical methods. Six compounds, 2, 3, 5, and 7-9, and 11 compounds, 1-9, bryodulcosigenin (10), and bryosigenin (11), respectively, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice and on Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA. All compounds tested showed marked anti-inflammatory effects, with 50% inhibitory doses (ID(50)) of 0.2-0.6 mg per ear. In addition, all of the compounds tested except for compound 5 showed potent inhibitory effects on EBV-EA induction (100% inhibition at 1 x 10(3) mol ratio/TPA).
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells at 10 molar ratio after 48 hrs relative to TPA
|
Human herpesvirus 4
|
100.0
%
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory and anti-tumor-promoting effects of cucurbitane glycosides from the roots of Bryonia dioica.
Year : 2002
Volume : 65
Issue : 2
First Page : 179
Last Page : 183
Authors : Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Toriumi M, Koike K, Kimura Y, Nikaido T, Aoi W, Nishino H, Takido M.
Abstract : Seven new triterpene glycosides, bryoniosides A-G (1-7), have been isolated along with two known triterpene glycosides, cabenoside D (8) and bryoamaride (9), from a methanol extract of the roots of Bryoniadioica. The structures of 1-7 were determined on the basis of spectroscopic and chemical methods. Six compounds, 2, 3, 5, and 7-9, and 11 compounds, 1-9, bryodulcosigenin (10), and bryosigenin (11), respectively, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice and on Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA. All compounds tested showed marked anti-inflammatory effects, with 50% inhibitory doses (ID(50)) of 0.2-0.6 mg per ear. In addition, all of the compounds tested except for compound 5 showed potent inhibitory effects on EBV-EA induction (100% inhibition at 1 x 10(3) mol ratio/TPA).
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells assessed as early antigen activation after 48 hrs relative to control
|
Human herpesvirus 4
|
400.0
molar ratio
|
|
Journal : J. Nat. Prod.
Title : Chemical constituents of Calophyllum brasiliense. 2. Structure of three new coumarins and cancer chemopreventive activity of 4-substituted coumarins.
Year : 2003
Volume : 66
Issue : 3
First Page : 368
Last Page : 371
Authors : Ito C, Itoigawa M, Mishina Y, Filho VC, Enjo F, Tokuda H, Nishino H, Furukawa H.
Abstract : Continuing our search for cancer chemopreventive agents from natural sources, we examined constituents of the stem bark of Calophyllum brasiliense. Three new 4-substituted coumarins named brasimarins A (2), B (3), and C (4) were isolated and characterized, along with 11 known coumarins belonging to the calanolides or inophyllums. We also discuss the inhibitory effects of these coumarins on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells.
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells at 32 nmol after 48 hrs relative to TPA
|
Human herpesvirus 4
|
9.1
%
|
|
Journal : J. Nat. Prod.
Title : Chemical constituents of Garcinia fusca: structure elucidation of eight new xanthones and their cancer chemopreventive activity.
Year : 2003
Volume : 66
Issue : 2
First Page : 200
Last Page : 205
Authors : Ito C, Itoigawa M, Takakura T, Ruangrungsi N, Enjo F, Tokuda H, Nishino H, Furukawa H.
Abstract : We describe the isolation and spectrometric structure elucidation of eight new xanthones, fuscaxanthone A (1), B (2), C (3), D (4), E (5), F (6), G (7), and H (8), together with eight known xanthones from the stem bark of Garcinia fusca collected in Thailand. All the new xanthones were shown to have a terpenoid (prenyl and/or geranyl) side chain(s) in their molecules. We also present the results of a primary screening of the inhibitory effects of eight xanthones (9-16) isolated as major components of this plant on 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus early antigen activation in Raji cells.
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells at 16 nmol after 48 hrs relative to TPA
|
Human herpesvirus 4
|
34.3
%
|
|
Journal : J. Nat. Prod.
Title : Chemical constituents of Garcinia fusca: structure elucidation of eight new xanthones and their cancer chemopreventive activity.
Year : 2003
Volume : 66
Issue : 2
First Page : 200
Last Page : 205
Authors : Ito C, Itoigawa M, Takakura T, Ruangrungsi N, Enjo F, Tokuda H, Nishino H, Furukawa H.
Abstract : We describe the isolation and spectrometric structure elucidation of eight new xanthones, fuscaxanthone A (1), B (2), C (3), D (4), E (5), F (6), G (7), and H (8), together with eight known xanthones from the stem bark of Garcinia fusca collected in Thailand. All the new xanthones were shown to have a terpenoid (prenyl and/or geranyl) side chain(s) in their molecules. We also present the results of a primary screening of the inhibitory effects of eight xanthones (9-16) isolated as major components of this plant on 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus early antigen activation in Raji cells.
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells at 3.2 nmol after 48 hrs relative to TPA
|
Human herpesvirus 4
|
82.7
%
|
|
Journal : J. Nat. Prod.
Title : Chemical constituents of Garcinia fusca: structure elucidation of eight new xanthones and their cancer chemopreventive activity.
Year : 2003
Volume : 66
Issue : 2
First Page : 200
Last Page : 205
Authors : Ito C, Itoigawa M, Takakura T, Ruangrungsi N, Enjo F, Tokuda H, Nishino H, Furukawa H.
Abstract : We describe the isolation and spectrometric structure elucidation of eight new xanthones, fuscaxanthone A (1), B (2), C (3), D (4), E (5), F (6), G (7), and H (8), together with eight known xanthones from the stem bark of Garcinia fusca collected in Thailand. All the new xanthones were shown to have a terpenoid (prenyl and/or geranyl) side chain(s) in their molecules. We also present the results of a primary screening of the inhibitory effects of eight xanthones (9-16) isolated as major components of this plant on 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus early antigen activation in Raji cells.
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells at 0.32 nmol after 48 hrs relative to TPA
|
Human herpesvirus 4
|
100.0
%
|
|
Journal : J. Nat. Prod.
Title : Chemical constituents of Garcinia fusca: structure elucidation of eight new xanthones and their cancer chemopreventive activity.
Year : 2003
Volume : 66
Issue : 2
First Page : 200
Last Page : 205
Authors : Ito C, Itoigawa M, Takakura T, Ruangrungsi N, Enjo F, Tokuda H, Nishino H, Furukawa H.
Abstract : We describe the isolation and spectrometric structure elucidation of eight new xanthones, fuscaxanthone A (1), B (2), C (3), D (4), E (5), F (6), G (7), and H (8), together with eight known xanthones from the stem bark of Garcinia fusca collected in Thailand. All the new xanthones were shown to have a terpenoid (prenyl and/or geranyl) side chain(s) in their molecules. We also present the results of a primary screening of the inhibitory effects of eight xanthones (9-16) isolated as major components of this plant on 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus early antigen activation in Raji cells.
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells per 32 pmol TPA after 48 hrs
|
Human herpesvirus 4
|
400.0
molar ratio
|
|
Journal : J. Nat. Prod.
Title : Chemical constituents of Garcinia fusca: structure elucidation of eight new xanthones and their cancer chemopreventive activity.
Year : 2003
Volume : 66
Issue : 2
First Page : 200
Last Page : 205
Authors : Ito C, Itoigawa M, Takakura T, Ruangrungsi N, Enjo F, Tokuda H, Nishino H, Furukawa H.
Abstract : We describe the isolation and spectrometric structure elucidation of eight new xanthones, fuscaxanthone A (1), B (2), C (3), D (4), E (5), F (6), G (7), and H (8), together with eight known xanthones from the stem bark of Garcinia fusca collected in Thailand. All the new xanthones were shown to have a terpenoid (prenyl and/or geranyl) side chain(s) in their molecules. We also present the results of a primary screening of the inhibitory effects of eight xanthones (9-16) isolated as major components of this plant on 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus early antigen activation in Raji cells.
|
Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced EBV-early antigen activation in human Raji cells assessed per 32 pmol TPA by immunofluorescence technique
|
Human herpesvirus 4
|
400.0
molar ratio
|
|
Journal : J. Nat. Prod.
Title : Lucidenic acids P and Q, methyl lucidenate P, and other triterpenoids from the fungus Ganoderma lucidum and their inhibitory effects on Epstein-Barr virus activation.
Year : 2003
Volume : 66
Issue : 12
First Page : 1582
Last Page : 1585
Authors : Iwatsuki K, Akihisa T, Tokuda H, Ukiya M, Oshikubo M, Kimura Y, Asano T, Nomura A, Nishino H.
Abstract : A new triterpene acid, lucidenic acid P (1a), and two new triterpene acid methyl esters, methyl lucidenates P (1b) and Q (2b), were isolated and characterized from the fruiting body of the fungus Ganoderma lucidum. Their structures were elucidated on the basis of spectroscopic methods. In addition, eight known triterpene acids, lucidenic acids A (3a), C (4a), D(2) (5a), E(2) (6a), and F (7a) and ganoderic acids E (9a), F (10a), and T-Q (11a), and six known triterpene acid methyl esters, methyl lucidenates A (3b), D(2) (5b), E(2) (6b), F (7b), and L (8b) and methyl ganoderate F (10b), were isolated and identified from the fungus. All of the triterpenoids, with the exception of 7a, were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor promoters. All of the compounds tested showed potent inhibitory effects on EBV-EA induction (96-100% inhibition at 1 x 10(3) mol ratio/TPA).
|
Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced EBV-early antigen activation in human Raji cells assessed per 32 pmol TPA
|
Human herpesvirus 4
|
400.0
molar ratio
|
|
Journal : J. Nat. Prod.
Title : New cinnamylphenols from Dalbergia species with cancer chemopreventive activity.
Year : 2003
Volume : 66
Issue : 12
First Page : 1574
Last Page : 1577
Authors : Ito C, Itoigawa M, Kanematsu T, Ruangrungsi N, Higashihara H, Tokuda H, Nishino H, Furukawa H.
Abstract : Five new cinnamylphenols (1,3-diphenylpropenes), dalberatins A (1), B (2), C (3), D (4), and E (5), were isolated from plants of the Dalbergia species. They were characterized and tested for their inhibitory activities against Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The cinnamylphenols were found to show remarkably potent activities. The result of the present investigation indicated that some of these cinnamylphenols might be valuable as potential cancer chemopreventive agents (anti-tumor promoters).
|
Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced EBV-early antigen activation in human Raji cells assessed as EA activation per 32 pmol TPA after 48 hrs
|
Human herpesvirus 4
|
400.0
molar ratio
|
|
Journal : J. Nat. Prod.
Title : Cancer chemopreventive agents. New depsidones from Garcinia plants.
Year : 2001
Volume : 64
Issue : 2
First Page : 147
Last Page : 150
Authors : Ito C, Itoigawa M, Mishina Y, Tomiyasu H, Litaudon M, Cosson JP, Mukainaka T, Tokuda H, Nishino H, Furukawa H.
Abstract : In a search for cancer chemopreventive agents from natural sources, chemical constituents of two kinds of Garcinia plants, Garcinia neglecta and Garcinia puat, collected in New Caledonia, were examined. Five new depsidones, garcinisidone-B (2), -C (3), -D (4), -E (5), and -F (6), were isolated, and their structures were determined by spectrometric analyses. Inhibitory effects of these depsidones on EBV-EA activation induced by TPA in Raji cells were also demonstrated.
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells relative to TPA
|
Human herpesvirus 4
|
397.0
molar ratio
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory, anti-tumor-promoting, and cytotoxic activities of constituents of marigold (Calendula officinalis) flowers.
Year : 2006
Volume : 69
Issue : 12
First Page : 1692
Last Page : 1696
Authors : Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Suzuki T, Kimura Y.
Abstract : Ten oleanane-type triterpene glycosides, 1-10, including four new compounds, calendulaglycoside A 6'-O-methyl ester (2), calendulaglycoside A 6'-O-n-butyl ester (3), calendulaglycoside B 6'-O-n-butyl ester (5), and calendulaglycoside C 6'-O-n-butyl ester (8), along with five known flavonol glycosides, 11-15, were isolated from the flowers of marigold (Calendula officinalis). Upon evaluation of compounds 1-9 for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds, except for 1, exhibited marked anti-inflammatory activity, with ID50 values of 0.05-0.20 mg per ear. In addition, when 1-15 were evaluated against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA, compounds 1-10 exhibited moderate inhibitory effects (IC50 values of 471-487 mol ratio/32 pmol TPA). Furthermore, upon evaluation of the cytotoxic activity against human cancer cell lines in vitro in the NCI Developmental Therapeutics Program, two triterpene glycosides, 9 and 10, exhibited their most potent cytotoxic effects against colon cancer, leukemia, and melanoma cells.
|
Inhibition of 12-O-tetradecanoylphorbol 13-acetate-induced Epstein-Barr virus early antigen activation in human Raji cells assessed as EA induction at 1000 mol ratio relative to TPA
|
Human herpesvirus 4
|
9.0
%
|
|
Journal : J. Nat. Prod.
Title : Potential antitumor-promoting diterpenoids from the stem bark of Picea glehni.
Year : 2000
Volume : 63
Issue : 6
First Page : 817
Last Page : 820
Authors : Kinouchi Y, Ohtsu H, Tokuda H, Nishino H, Matsunaga S, Tanaka R.
Abstract : A novel rearranged labdane-type diterpenoid, 19(4-->3)abeo-8alpha, 13(S)-epoxylabda-4(18),14-diene (1), and two new abietane-type diterpenoids, 19-nor-abieta-4(18),8,11,13-tetraen-7-one (2) and 12-hydroxydehydroabietic acid (3) were isolated from the stem bark of Picea glehni, together with seven known diterpenoids-13-epimanoyl oxide (4), dehydroabietic acid (5), (11E)-14, 15-bisnor-8alpha-hydroxy-11-labden-13-one (6), abieta-8,11, 13-trien-7-one (7), 9alpha,13alpha-epidioxyabiet-8(14)-en-18-oic acid (8), 9,10alpha-epoxy-9,10-seco-abieta-8,11,13-trien-18-oic acid (9), and methyl 15-hydroxy-7-oxo-dehydroabietate (10). Compounds 5-8 and 10 showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.
|
Inhibition of 12-O-tetradecanoylphorbol 13-acetate-induced Epstein-Barr virus early antigen activation in human Raji cells assessed as EA induction at 500 mol ratio relative to TPA
|
Human herpesvirus 4
|
34.0
%
|
|
Journal : J. Nat. Prod.
Title : Potential antitumor-promoting diterpenoids from the stem bark of Picea glehni.
Year : 2000
Volume : 63
Issue : 6
First Page : 817
Last Page : 820
Authors : Kinouchi Y, Ohtsu H, Tokuda H, Nishino H, Matsunaga S, Tanaka R.
Abstract : A novel rearranged labdane-type diterpenoid, 19(4-->3)abeo-8alpha, 13(S)-epoxylabda-4(18),14-diene (1), and two new abietane-type diterpenoids, 19-nor-abieta-4(18),8,11,13-tetraen-7-one (2) and 12-hydroxydehydroabietic acid (3) were isolated from the stem bark of Picea glehni, together with seven known diterpenoids-13-epimanoyl oxide (4), dehydroabietic acid (5), (11E)-14, 15-bisnor-8alpha-hydroxy-11-labden-13-one (6), abieta-8,11, 13-trien-7-one (7), 9alpha,13alpha-epidioxyabiet-8(14)-en-18-oic acid (8), 9,10alpha-epoxy-9,10-seco-abieta-8,11,13-trien-18-oic acid (9), and methyl 15-hydroxy-7-oxo-dehydroabietate (10). Compounds 5-8 and 10 showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.
|
Inhibition of 12-O-tetradecanoylphorbol 13-acetate-induced Epstein-Barr virus early antigen activation in human Raji cells assessed as EA induction at 100 mol ratio relative to TPA
|
Human herpesvirus 4
|
82.0
%
|
|
Journal : J. Nat. Prod.
Title : Potential antitumor-promoting diterpenoids from the stem bark of Picea glehni.
Year : 2000
Volume : 63
Issue : 6
First Page : 817
Last Page : 820
Authors : Kinouchi Y, Ohtsu H, Tokuda H, Nishino H, Matsunaga S, Tanaka R.
Abstract : A novel rearranged labdane-type diterpenoid, 19(4-->3)abeo-8alpha, 13(S)-epoxylabda-4(18),14-diene (1), and two new abietane-type diterpenoids, 19-nor-abieta-4(18),8,11,13-tetraen-7-one (2) and 12-hydroxydehydroabietic acid (3) were isolated from the stem bark of Picea glehni, together with seven known diterpenoids-13-epimanoyl oxide (4), dehydroabietic acid (5), (11E)-14, 15-bisnor-8alpha-hydroxy-11-labden-13-one (6), abieta-8,11, 13-trien-7-one (7), 9alpha,13alpha-epidioxyabiet-8(14)-en-18-oic acid (8), 9,10alpha-epoxy-9,10-seco-abieta-8,11,13-trien-18-oic acid (9), and methyl 15-hydroxy-7-oxo-dehydroabietate (10). Compounds 5-8 and 10 showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.
|
Inhibition of 12-O-tetradecanoylphorbol 13-acetate-induced Epstein-Barr virus early antigen activation in human Raji cells assessed as EA induction at 10 mol ratio relative to TPA
|
Human herpesvirus 4
|
100.0
%
|
|
Journal : J. Nat. Prod.
Title : Potential antitumor-promoting diterpenoids from the stem bark of Picea glehni.
Year : 2000
Volume : 63
Issue : 6
First Page : 817
Last Page : 820
Authors : Kinouchi Y, Ohtsu H, Tokuda H, Nishino H, Matsunaga S, Tanaka R.
Abstract : A novel rearranged labdane-type diterpenoid, 19(4-->3)abeo-8alpha, 13(S)-epoxylabda-4(18),14-diene (1), and two new abietane-type diterpenoids, 19-nor-abieta-4(18),8,11,13-tetraen-7-one (2) and 12-hydroxydehydroabietic acid (3) were isolated from the stem bark of Picea glehni, together with seven known diterpenoids-13-epimanoyl oxide (4), dehydroabietic acid (5), (11E)-14, 15-bisnor-8alpha-hydroxy-11-labden-13-one (6), abieta-8,11, 13-trien-7-one (7), 9alpha,13alpha-epidioxyabiet-8(14)-en-18-oic acid (8), 9,10alpha-epoxy-9,10-seco-abieta-8,11,13-trien-18-oic acid (9), and methyl 15-hydroxy-7-oxo-dehydroabietate (10). Compounds 5-8 and 10 showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.
|
Inhibition of TPA-induced EBV early antigen activation at 32 uM
|
Human herpesvirus 4
|
91.0
%
|
|
Journal : J. Nat. Prod.
Title : The taiwaniaquinoids: a review.
Year : 2010
Volume : 73
Issue : 2
First Page : 284
Last Page : 298
Authors : Majetich G, Shimkus JM.
Abstract : A comprehensive overview of the taiwaniaquinoid family of natural products is presented. A summary of the isolation, biosynthesis, and biological activity of these compounds is followed by a discussion of various synthetic strategies to the skeletal framework and a detailed discussion of 12 published syntheses of members of this family. This review covers the literature from the discovery of the first taiwaniaquinoid in 1995 until June 2009.
|
Inhibition of TPA-induced EBV early antigen activation at 16 uM
|
Human herpesvirus 4
|
66.0
%
|
|
Journal : J. Nat. Prod.
Title : The taiwaniaquinoids: a review.
Year : 2010
Volume : 73
Issue : 2
First Page : 284
Last Page : 298
Authors : Majetich G, Shimkus JM.
Abstract : A comprehensive overview of the taiwaniaquinoid family of natural products is presented. A summary of the isolation, biosynthesis, and biological activity of these compounds is followed by a discussion of various synthetic strategies to the skeletal framework and a detailed discussion of 12 published syntheses of members of this family. This review covers the literature from the discovery of the first taiwaniaquinoid in 1995 until June 2009.
|
Inhibition of TPA-induced EBV early antigen activation at 3.2 uM
|
Human herpesvirus 4
|
18.0
%
|
|
Journal : J. Nat. Prod.
Title : The taiwaniaquinoids: a review.
Year : 2010
Volume : 73
Issue : 2
First Page : 284
Last Page : 298
Authors : Majetich G, Shimkus JM.
Abstract : A comprehensive overview of the taiwaniaquinoid family of natural products is presented. A summary of the isolation, biosynthesis, and biological activity of these compounds is followed by a discussion of various synthetic strategies to the skeletal framework and a detailed discussion of 12 published syntheses of members of this family. This review covers the literature from the discovery of the first taiwaniaquinoid in 1995 until June 2009.
|
Inhibition of TPA-induced EBV early antigen activation at 0.32 uM
|
Human herpesvirus 4
|
0.0
%
|
|
Journal : J. Nat. Prod.
Title : The taiwaniaquinoids: a review.
Year : 2010
Volume : 73
Issue : 2
First Page : 284
Last Page : 298
Authors : Majetich G, Shimkus JM.
Abstract : A comprehensive overview of the taiwaniaquinoid family of natural products is presented. A summary of the isolation, biosynthesis, and biological activity of these compounds is followed by a discussion of various synthetic strategies to the skeletal framework and a detailed discussion of 12 published syntheses of members of this family. This review covers the literature from the discovery of the first taiwaniaquinoid in 1995 until June 2009.
|
Cytotoxicity against human Raji cells assessed as cell viability at 1000 molar ratio
|
Homo sapiens
|
70.0
%
|
|
Journal : J. Nat. Prod.
Title : Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos.
Year : 2009
Volume : 72
Issue : 10
First Page : 1786
Last Page : 1792
Authors : Akihisa T, Uchiyama E, Kikuchi T, Tokuda H, Suzuki T, Kimura Y.
Abstract : Nine new (1, 3, 5, 8, 12, 13, 15, 17, and 18) and nine known (2, 4, 6, 7, 9-11, 14, and 16) lanostane-type triterpene acids and a known diterpene acid (19) were isolated from the epidermis of the sclerotia of Poria cocos. The structures of the new compounds were established as 16alpha,27-dihydroxydehyrotrametenoic acid (1), 25-hydroxy-3-epitumulosic acid (3), 16alpha,25-dihydroxyeburiconic acid (5), 25-methoxyporicoic acid A (8), 26-hydroxyporicoic acid DM (12), 25-hydroxyporicoic acid C (13), poricoic acid GM (15), poricoic acid HM (17), and 6,7-dehydroporicoic acid H (18), on the basis of spectroscopic methods. On evaluation of the nine new and two of the known compounds, 4 and 19, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds exhibited inhibitory effects, with IC(50) values in the range 187-348 mol ratio/32 pmol TPA. In addition, compound 8 exhibited an inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Further, 17 compounds, 1-14, 16, 18, and 19, were evaluated for their cytotoxic activity against two human tumor cell lines, HL60 (leukemia) and CRL1579 (melanoma).
|
Inhibition of TPA-induced EBV early antigen activation in human Raji cells relative to TPA
|
Human herpesvirus 4
|
397.0
molar ratio
|
|
Journal : J. Nat. Prod.
Title : Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos.
Year : 2009
Volume : 72
Issue : 10
First Page : 1786
Last Page : 1792
Authors : Akihisa T, Uchiyama E, Kikuchi T, Tokuda H, Suzuki T, Kimura Y.
Abstract : Nine new (1, 3, 5, 8, 12, 13, 15, 17, and 18) and nine known (2, 4, 6, 7, 9-11, 14, and 16) lanostane-type triterpene acids and a known diterpene acid (19) were isolated from the epidermis of the sclerotia of Poria cocos. The structures of the new compounds were established as 16alpha,27-dihydroxydehyrotrametenoic acid (1), 25-hydroxy-3-epitumulosic acid (3), 16alpha,25-dihydroxyeburiconic acid (5), 25-methoxyporicoic acid A (8), 26-hydroxyporicoic acid DM (12), 25-hydroxyporicoic acid C (13), poricoic acid GM (15), poricoic acid HM (17), and 6,7-dehydroporicoic acid H (18), on the basis of spectroscopic methods. On evaluation of the nine new and two of the known compounds, 4 and 19, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds exhibited inhibitory effects, with IC(50) values in the range 187-348 mol ratio/32 pmol TPA. In addition, compound 8 exhibited an inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Further, 17 compounds, 1-14, 16, 18, and 19, were evaluated for their cytotoxic activity against two human tumor cell lines, HL60 (leukemia) and CRL1579 (melanoma).
|
Inhibition of TPA-induced EBV early antigen activation in human Raji cells at 10 molar relative to TPA
|
Human herpesvirus 4
|
100.0
%
|
|
Journal : J. Nat. Prod.
Title : Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos.
Year : 2009
Volume : 72
Issue : 10
First Page : 1786
Last Page : 1792
Authors : Akihisa T, Uchiyama E, Kikuchi T, Tokuda H, Suzuki T, Kimura Y.
Abstract : Nine new (1, 3, 5, 8, 12, 13, 15, 17, and 18) and nine known (2, 4, 6, 7, 9-11, 14, and 16) lanostane-type triterpene acids and a known diterpene acid (19) were isolated from the epidermis of the sclerotia of Poria cocos. The structures of the new compounds were established as 16alpha,27-dihydroxydehyrotrametenoic acid (1), 25-hydroxy-3-epitumulosic acid (3), 16alpha,25-dihydroxyeburiconic acid (5), 25-methoxyporicoic acid A (8), 26-hydroxyporicoic acid DM (12), 25-hydroxyporicoic acid C (13), poricoic acid GM (15), poricoic acid HM (17), and 6,7-dehydroporicoic acid H (18), on the basis of spectroscopic methods. On evaluation of the nine new and two of the known compounds, 4 and 19, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds exhibited inhibitory effects, with IC(50) values in the range 187-348 mol ratio/32 pmol TPA. In addition, compound 8 exhibited an inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Further, 17 compounds, 1-14, 16, 18, and 19, were evaluated for their cytotoxic activity against two human tumor cell lines, HL60 (leukemia) and CRL1579 (melanoma).
|
Inhibition of TPA-induced EBV early antigen activation in human Raji cells at 100 molar relative to TPA
|
Human herpesvirus 4
|
82.1
%
|
|
Journal : J. Nat. Prod.
Title : Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos.
Year : 2009
Volume : 72
Issue : 10
First Page : 1786
Last Page : 1792
Authors : Akihisa T, Uchiyama E, Kikuchi T, Tokuda H, Suzuki T, Kimura Y.
Abstract : Nine new (1, 3, 5, 8, 12, 13, 15, 17, and 18) and nine known (2, 4, 6, 7, 9-11, 14, and 16) lanostane-type triterpene acids and a known diterpene acid (19) were isolated from the epidermis of the sclerotia of Poria cocos. The structures of the new compounds were established as 16alpha,27-dihydroxydehyrotrametenoic acid (1), 25-hydroxy-3-epitumulosic acid (3), 16alpha,25-dihydroxyeburiconic acid (5), 25-methoxyporicoic acid A (8), 26-hydroxyporicoic acid DM (12), 25-hydroxyporicoic acid C (13), poricoic acid GM (15), poricoic acid HM (17), and 6,7-dehydroporicoic acid H (18), on the basis of spectroscopic methods. On evaluation of the nine new and two of the known compounds, 4 and 19, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds exhibited inhibitory effects, with IC(50) values in the range 187-348 mol ratio/32 pmol TPA. In addition, compound 8 exhibited an inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Further, 17 compounds, 1-14, 16, 18, and 19, were evaluated for their cytotoxic activity against two human tumor cell lines, HL60 (leukemia) and CRL1579 (melanoma).
|
Inhibition of TPA-induced EBV early antigen activation in human Raji cells at 1000 molar relative to TPA
|
Human herpesvirus 4
|
8.6
%
|
|
Journal : J. Nat. Prod.
Title : Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos.
Year : 2009
Volume : 72
Issue : 10
First Page : 1786
Last Page : 1792
Authors : Akihisa T, Uchiyama E, Kikuchi T, Tokuda H, Suzuki T, Kimura Y.
Abstract : Nine new (1, 3, 5, 8, 12, 13, 15, 17, and 18) and nine known (2, 4, 6, 7, 9-11, 14, and 16) lanostane-type triterpene acids and a known diterpene acid (19) were isolated from the epidermis of the sclerotia of Poria cocos. The structures of the new compounds were established as 16alpha,27-dihydroxydehyrotrametenoic acid (1), 25-hydroxy-3-epitumulosic acid (3), 16alpha,25-dihydroxyeburiconic acid (5), 25-methoxyporicoic acid A (8), 26-hydroxyporicoic acid DM (12), 25-hydroxyporicoic acid C (13), poricoic acid GM (15), poricoic acid HM (17), and 6,7-dehydroporicoic acid H (18), on the basis of spectroscopic methods. On evaluation of the nine new and two of the known compounds, 4 and 19, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds exhibited inhibitory effects, with IC(50) values in the range 187-348 mol ratio/32 pmol TPA. In addition, compound 8 exhibited an inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Further, 17 compounds, 1-14, 16, 18, and 19, were evaluated for their cytotoxic activity against two human tumor cell lines, HL60 (leukemia) and CRL1579 (melanoma).
|
Inhibition of TPA-induced EBV early antigen activation in human Raji cells at 500 molar relative to TPA
|
Human herpesvirus 4
|
34.2
%
|
|
Journal : J. Nat. Prod.
Title : Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos.
Year : 2009
Volume : 72
Issue : 10
First Page : 1786
Last Page : 1792
Authors : Akihisa T, Uchiyama E, Kikuchi T, Tokuda H, Suzuki T, Kimura Y.
Abstract : Nine new (1, 3, 5, 8, 12, 13, 15, 17, and 18) and nine known (2, 4, 6, 7, 9-11, 14, and 16) lanostane-type triterpene acids and a known diterpene acid (19) were isolated from the epidermis of the sclerotia of Poria cocos. The structures of the new compounds were established as 16alpha,27-dihydroxydehyrotrametenoic acid (1), 25-hydroxy-3-epitumulosic acid (3), 16alpha,25-dihydroxyeburiconic acid (5), 25-methoxyporicoic acid A (8), 26-hydroxyporicoic acid DM (12), 25-hydroxyporicoic acid C (13), poricoic acid GM (15), poricoic acid HM (17), and 6,7-dehydroporicoic acid H (18), on the basis of spectroscopic methods. On evaluation of the nine new and two of the known compounds, 4 and 19, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds exhibited inhibitory effects, with IC(50) values in the range 187-348 mol ratio/32 pmol TPA. In addition, compound 8 exhibited an inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Further, 17 compounds, 1-14, 16, 18, and 19, were evaluated for their cytotoxic activity against two human tumor cell lines, HL60 (leukemia) and CRL1579 (melanoma).
|
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
9.952
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
pIC50 values for sodium fluorescein (10 uM) uptake in OATP1B1-transfected CHO cells
|
Cricetulus griseus
|
616.6
nM
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Ki values for sodium fluorescein (10 uM) uptake in OATP1B1-transfected CHO cells
|
Cricetulus griseus
|
340.0
nM
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
13.45
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
24.57
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
-4.71
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
3.018
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
-0.01
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
-0.02
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
-0.01
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
-0.02
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
