|
Mammalian cell cytotoxicity test in chinese hamster V79 cells (clonogenic cytotoxicity)
|
None
|
500.0
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity, and antimicrobial activity.
Year : 1992
Volume : 35
Issue : 25
First Page : 4745
Last Page : 4750
Authors : Suto MJ, Domagala JM, Roland GE, Mailloux GB, Cohen MA.
Abstract : Fluoroquinolones are potent inhibitors of bacterial topoisomerase II (DNA gyrase). They can also inhibit eukaryotic topoisomerases, which could possibly lead to clastogenicity and/or cellular toxicity. Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the fluoroquinolones and the potential of these compounds to induce micronuclei, a genetic toxicity endpoint. In an effort to identify potent nontoxic quinolone antibacterials, we have examined the structural features of the fluoroquinolones associated with mammalian cell cytotoxicity. An investigation of a wide variety of substituents at the 1, 5, 7, and 8 positions of a quinolone nucleus was conducted. The results indicate that no one position has a controlling effect on the observed cytotoxicity. Instead, a combination of the various substituents contributes to the effects seen. Certain trends were apparent, such as the fact that compounds with pyrrolidines at the R-7 position were more cytotoxic than those with piperazines, and halogens at R-8 (X-position) were associated with more cytotoxicity relative to hydrogen. A general trend also existed between the cytotoxicity of the compounds and their Gram-positive antibacterial activity. A detailed comparison between the various groups and positional variations as they controlled the cytotoxicity and antibacterial activity is presented.
|
Concentration of compound needed to produce linear DNA at an intensity relative to oxolinic acid at 10 ug/mL was measured on Escherichia coli for gyrase-drug induced cleavage,.
|
Escherichia coli
|
5.5
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Enantiomers of 1-ethyl-7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-6,8-difluoro-1,4- dihydro-4-oxo-3-quinoline-carboxylic acid: preparation and biological activity.
Year : 1987
Volume : 30
Issue : 10
First Page : 1711
Last Page : 1715
Authors : Culbertson TP, Domagala JM, Nichols JB, Priebe S, Skeean RW.
|
Inhibition of [3H]muscimol binding to GABA A receptor 4-biphenylacetic acid at 10 e-4 M
|
None
|
20.0
nM
|
|
Journal : J. Med. Chem.
Title : Quinolone antimicrobial agents substituted with morpholines at the 7-position. Syntheses and structure-activity relationships.
Year : 1993
Volume : 36
Issue : 10
First Page : 1356
Last Page : 1363
Authors : Araki K, Kuroda T, Uemori S, Moriguchi A, Ikeda Y, Hirayama F, Yokoyama Y, Iwao E, Yakushiji T.
Abstract : A series of novel 7-substituted 1-cyclopropyl-6,8-difluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids have been prepared and tested for antibacterial activities and for convulsive activities in combination with nonsteroidal antiinflammatory drug. Structure-activity relationships revealed that 7-(2-(aminomethyl)morpholino) derivative 28 had a better Gram-positive activity than the reference quinolones, such as ciprofloxacin, norfloxacin, and ofloxacin. Its Gram-negative activity was equipotent with those of norfloxacin and ofloxacin but was inferior to that of ciprofloxacin. In mouse systemic infection models, 28 showed an excellent therapeutic efficacy which might result from the potent antibacterial activity and suitable physicochemical properties. Convulsive activities of 7-morpholino derivatives in combination with nonsteroidal antiinflammatory drug fenbufen or its metabolite biphenylacetic acid markedly diminished as compared to those of 7-piperazino derivatives in the electrophysiological, biochemical, and behavioral experiments. These results suggest that 28 (Y-26611) is a novel quinolone with reduced neurotoxic excitatory adverse reaction.
|
Inhibitory concentration in supercoiling inhibition Escherichia coli DNA gyrase assay
|
Escherichia coli
|
5.5
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay.
Year : 1986
Volume : 29
Issue : 3
First Page : 394
Last Page : 404
Authors : Domagala JM, Hanna LD, Heifetz CL, Hutt MP, Mich TF, Sanchez JP, Solomon M.
Abstract : A series of 60 newly synthesized and known quinolone antibacterials, including quinoline- and 1,8-naphthyridine-3-carboxylic acids, pyrido[2,3-d]pyrimidine-6-carboxylic acids, and some monocyclic 4-pyridone-3-carboxylic acids, were tested and compared in a newly established, easy to perform, DNA gyrase assay. The results were correlated with minimum inhibitory concentrations (MICs) against a variety of organisms. Among the known quinolones were 14 clinically significant drugs (oxolinic acid, norfloxacin, ciprofloxacin, enoxacin, etc.) which were used as standards and compared side-by-side. The study focused on the changes in DNA gyrase inhibition brought about by certain features of the molecules, namely, the C6-fluorine or the nature of the C7 substituent. The intrinsic gyrase inhibition of the fused parent rings, quinoline vs. naphthyridine vs. pyrido[2,3-d]pyrimidine, was also explored. In all cases, loss of enzyme inhibition produced poor MICs, but some compounds with good DNA gyrase inhibition did not correspondingly inhibit bacterial growth. Possible explanations for this phenomena and the benefits of a DNA gyrase-MIC strategy for developing future structure-activity relationships are discussed.
|
Supercoiling inhibition activity DNA gyrase isolated from Escherichia coli H560
|
Escherichia coli
|
1.0
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Asymmetric synthesis and properties of the enantiomers of the antibacterial agent 7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6- fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride.
Year : 1988
Volume : 31
Issue : 8
First Page : 1586
Last Page : 1590
Authors : Rosen T, Chu DT, Lico IM, Fernandes PB, Shen L, Borodkin S, Pernet AG.
Abstract : Compound 1 [7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-f luoro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride] is a potent member of the quinolonecarboxylic acid class of antibacterial agents and is currently undergoing clinical evaluation. We have developed efficient asymmetric syntheses of the enantiomers of this agent. The S-(+) enantiomer 1a is 1-2 log2 dilutions more active than the R-(-) enantiomer 1b against aerobic bacteria and 1-2 or more log2 dilutions more active against anaerobic bacteria in vitro. The enantiomer 1a shows significantly better in vivo activity in a Pseudomonas aeruginosa mouse protection model compared to racemic 1. Coupled with the improved solubility profile of 1a relative to racemic material, these features may be of practical significance from a clinical standpoint.
|
Inhibition constant against DNA Gyrase isolated from Escherichia coli
|
Escherichia coli
|
1.0
ug ml-1
|
|
Journal : J. Med. Chem.
Title : Chiral DNA gyrase inhibitors. 2. Asymmetric synthesis and biological activity of the enantiomers of 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (ofloxacin).
Year : 1987
Volume : 30
Issue : 12
First Page : 2283
Last Page : 2286
Authors : Mitscher LA, Sharma PN, Chu DT, Shen LL, Pernet AG.
Abstract : A short and efficient synthesis, starting with (R)- and (S)-alaninol, of the two optical antipodes of the quinolone antimicrobial agent ofloxacin has been devised. Testing in vitro of the products against a range of bacteria and in an assay system incorporating purified DNA gyrase from different bacterial species demonstrates that the S-(-) enantiomer is substantially the more active.
|
Inhibition constant against DNA Gyrase isolated from Micrococcus luteus
|
Micrococcus luteus
|
72.0
ug ml-1
|
|
Journal : J. Med. Chem.
Title : Chiral DNA gyrase inhibitors. 2. Asymmetric synthesis and biological activity of the enantiomers of 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (ofloxacin).
Year : 1987
Volume : 30
Issue : 12
First Page : 2283
Last Page : 2286
Authors : Mitscher LA, Sharma PN, Chu DT, Shen LL, Pernet AG.
Abstract : A short and efficient synthesis, starting with (R)- and (S)-alaninol, of the two optical antipodes of the quinolone antimicrobial agent ofloxacin has been devised. Testing in vitro of the products against a range of bacteria and in an assay system incorporating purified DNA gyrase from different bacterial species demonstrates that the S-(-) enantiomer is substantially the more active.
|
Inhibition of DNA gyrase supercoiling in Escherichia coli ATCC 25922
|
Escherichia coli
|
600.0
nM
|
|
Journal : J. Med. Chem.
Title : Isothiazolopyridones: synthesis, structure, and biological activity of a new class of antibacterial agents.
Year : 2006
Volume : 49
Issue : 1
First Page : 39
Last Page : 42
Authors : Wiles JA, Hashimoto A, Thanassi JA, Cheng J, Incarvito CD, Deshpande M, Pucci MJ, Bradbury BJ.
Abstract : We report the syntheses of first-generation derivatives of isothiazolopyridones and their in vitro evaluation as antibacterial agents. These compounds, containing a novel heterocyclic nucleus composed of an isothiazolone fused to a quinolizin-4-one (at C-2 and C-3 of the quinolizin-4-one), were prepared using a sequence of seven synthetic transformations. The solid-state structure of 7-chloro-9-ethyl-1-thia-2,4a-diazacyclopenta[b]naphthalene-3,4-dione was determined by X-ray diffraction. The prepared derivatives of desfluoroisothiazolopyridones exhibited (a) antibacterial activity against Gram-negative and Gram-positive organisms, (b) inhibitory activities against DNA gyrase and topoisomerase IV, and (c) no inhibitory activity against human topoisomerase II.
|
Inhibition of Escherichia coli H560 DNA gyrase
|
Escherichia coli
|
1.0
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Tetramic and tetronic acids: an update on new derivatives and biological aspects.
Year : 2008
Volume : 16
Issue : 8
First Page : 4203
Last Page : 4221
Authors : Schobert R, Schlenk A.
Abstract : Significant developments in the isolation of tetramic acids and tetronic acids, in the elucidation of their biosyntheses and their biological activities and in laboratory syntheses are reviewed with a focus on those derivatives with medicinal and pharmacological relevance. Important new members of the title compound families isolated since the year 2000 are covered as well as new biological aspects of some earlier congeners.
|
Antibacterial activity against Escherichia coli at 100 ug/mL after 48 hrs by cup-plate method
|
Escherichia coli
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antibacterial activity against Escherichia coli at 50 ug/mL after 48 hrs by cup-plate method
|
Escherichia coli
|
220.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antibacterial activity against Escherichia coli at 25 ug/mL after 48 hrs by cup-plate method
|
Escherichia coli
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antibacterial activity against Bacillus cirrhosis at 100 ug/mL after 48 hrs by cup-plate method
|
Bacillus
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antibacterial activity against Bacillus cirrhosis at 50 ug/mL after 48 hrs by cup-plate method
|
Bacillus
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antibacterial activity against Bacillus cirrhosis at 25 ug/mL after 48 hrs by cup-plate method
|
Bacillus
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antifungal activity against Aspergillus niger at 100 ug/mL after 48 hrs by cup-plate method
|
Aspergillus niger
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antifungal activity against Aspergillus niger at 50 ug/mL after 48 hrs by cup-plate method
|
Aspergillus niger
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antifungal activity against Aspergillus niger at 25 ug/mL after 48 hrs by cup-plate method
|
Aspergillus niger
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antifungal activity against Rhizoctonia bataticola at 100 ug/mL after 48 hrs by cup-plate method
|
Rhizoctonia bataticola
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antifungal activity against Rhizoctonia bataticola at 50 ug/mL after 48 hrs by cup-plate method
|
Rhizoctonia bataticola
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Antifungal activity against Rhizoctonia bataticola at 25 ug/mL after 48 hrs by cup-plate method
|
Rhizoctonia bataticola
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins.
Year : 2008
Volume : 43
Issue : 10
First Page : 2178
Last Page : 2188
Authors : Kalkhambkar RG, Kulkarni GM, Kamanavalli CM, Premkumar N, Asdaq SM, Sun CM.
Abstract : A series of new fluorinated coumarins and 1-aza coumarins have been synthesized and the presence of fluorine in these molecules and its effect on their anti-microbial, anti-inflammatory and analgesic activities are discussed. The results of bioassay showed that these newly synthesized compounds containing fluorine exhibit moderate analgesic and excellent anti-inflammatory and potential anti-bacterial and anti-fungal activities, compared to the other halogenated compounds. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR, EI-MS, and FAB-MS. The ORTEP diagram of one of the compounds is reported herein.
|
Inhibition of Escherichia coli DNA gyraseB assessed as inhibition of pBR322 supercoiling by densitometry
|
Escherichia coli
|
90.0
nM
|
|
Inhibition of Escherichia coli DNA gyraseB assessed as inhibition of pBR322 supercoiling by densitometry
|
Escherichia coli
|
0.09
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design, synthesis, and biological evaluation of a novel series of quercetin diacylglucosides as potent anti-MRSA and anti-VRE agents.
Year : 2010
Volume : 20
Issue : 17
First Page : 5349
Last Page : 5352
Authors : Hossion AM, Otsuka N, Kandahary RK, Tsuchiya T, Ogawa W, Iwado A, Zamami Y, Sasaki K.
Abstract : A series of novel quercetin diacylglucosides were designed and first synthesized by Steglich esterification on the basis of MRSA strains inhibiting natural compound A. The in vitro inhibition of different multi-drug resistant bacterial strains and Escherichia coli DNA gyrase B was investigated. In the series, compound 10h was up to 128-fold more potent against vancomycin-resistant enterococci and more effective than A, which represents a promising new candidate as a potent anti-MRSA and anti-VRE agent.
|
PUBCHEM_BIOASSAY: A screen for inhibitors of the PhoP region in Salmonella Typhimurium using a modified counterscreen. (Class of assay: confirmatory) [Related pubchem assays: 2253, 1863, 1874 ]
|
None
|
890.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: A Counter Screen to identiry small molecule screen for inhibitors of the PhoP region in Salmonella Typhimurium. (Class of assay: confirmatory) [Related pubchem assays: 2253, 1863, 1981, 1874 ]
|
None
|
880.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: A small molecule screen for inhibitors of the PhoP region in Salmonella Typhimurium. (Class of assay: confirmatory) [Related pubchem assays: 2253, 1981, 1874 ]
|
None
|
510.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: A counter screen for small molecule screen for inhibitors of the PhoP region in Salmonella typhi. (Class of assay: confirmatory) [Related pubchem assays: 1850, 1864, 2252, 1985 ]
|
None
|
490.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: A small molecule screen for inhibitors of the PhoP region in Salmonella typhi. (Class of assay: confirmatory) [Related pubchem assays: 1864, 2252, 1985 ]
|
None
|
270.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: A screen for inhibitors of the PhoP region in Salmonella Typhi using a modified counterscreen. (Class of assay: confirmatory)
|
None
|
230.0
nM
|
|
Title : PubChem BioAssay data set
|
Inhibition of Escherichia coli DNA gyrase assessed as inhibition of pBR322 supercoiling by densitometry
|
Escherichia coli
|
90.0
nM
|
|
Journal : J. Med. Chem.
Title : Quercetin diacylglycoside analogues showing dual inhibition of DNA gyrase and topoisomerase IV as novel antibacterial agents.
Year : 2011
Volume : 54
Issue : 11
First Page : 3686
Last Page : 3703
Authors : Hossion AM, Zamami Y, Kandahary RK, Tsuchiya T, Ogawa W, Iwado A, Sasaki K.
Abstract : A structure-guided molecular design approach was used to optimize quercetin diacylglycoside analogues that inhibit bacterial DNA gyrase and topoisomerase IV and show potent antibacterial activity against a wide spectrum of relevant pathogens responsible for hospital- and community-acquired infections. In this paper, such novel 3,7-diacylquercetin, quercetin 6''-acylgalactoside, and quercetin 2'',6''-diacylgalactoside analogues of lead compound 1 were prepared to assess their target specificities and preferences in bacteria. The significant enzymatic inhibition of both Escherichia coli DNA gyrase and Staphylococcus aureus topoIV suggest that these compounds are dual inhibitors. Most of the investigated compounds exhibited pronounced inhibition with MIC values ranging from 0.13 to 128 μg/mL toward the growth of multidrug-resistant Gram-positive methicillin-resistant S. aureus, methicillin sensitive S. aureus, vancomycin-resistant enterococci (VRE), vancomycin intermediate S. aureus, and Streptococcus pneumoniae bacterial strains. Structure-activity relationship studies revealed that the acyl moiety was absolutely essential for activity against Gram-positive organisms. The most active compound 5i was 512-fold more potent than vancomycin and 16-32-fold more potent than 1 against VRE strains. It also has realistic in situ intestinal absorption in rats and showed very low acute toxicity in mice. So far, this compound can be regarded as a leading antibacterial agent.
|
Antitubercular activity against Mycobacterium tuberculosis
|
Mycobacterium tuberculosis
|
8.0
ug.mL-1
|
|
Journal : Med Chem Res
Title : Quinolone derivatives as antitubercular drugs
Year : 2013
Volume : 22
Issue : 3
First Page : 1029
Last Page : 1042
Authors : Asif M, Siddiqui AA, Husain A
|
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
97.94
%
|
|
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
|
99.94
%
|
|
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.
|
Antibacterial activity against Bacillus amyloliquefaciens at 25 ug/ml after overnight incubation by plate colony counting method relative to control
|
Bacillus amyloliquefaciens
|
89.0
%
|
|
Journal : Eur J Med Chem
Title : Design, synthesis and antimicrobial activities of thiouracil derivatives containing triazolo-thiadiazole as SecA inhibitors.
Year : 2017
Volume : 127
First Page : 159
Last Page : 165
Authors : Cui P, Li X, Zhu M, Wang B, Liu J, Chen H.
Abstract : A series of novel thiouracil derivatives containing a triazolo-thiadiazole moiety (7a-7l) have been synthesized by structural modifications on a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7d and 7g were also tested for their inhibitory activities against SecA ATPase due to their promising antimicrobial activities. The inhibitory activity of compound 7d was found to be higher than that of 2. Molecular docking work suggests that compound 7d might bind at a pocket close to the ATPase ATP-binding domain.
|
Antibacterial activity against Staphylococcus aureus at 25 ug/ml after overnight incubation by plate colony counting method relative to control
|
Staphylococcus aureus
|
86.0
%
|
|
Journal : Eur J Med Chem
Title : Design, synthesis and antimicrobial activities of thiouracil derivatives containing triazolo-thiadiazole as SecA inhibitors.
Year : 2017
Volume : 127
First Page : 159
Last Page : 165
Authors : Cui P, Li X, Zhu M, Wang B, Liu J, Chen H.
Abstract : A series of novel thiouracil derivatives containing a triazolo-thiadiazole moiety (7a-7l) have been synthesized by structural modifications on a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7d and 7g were also tested for their inhibitory activities against SecA ATPase due to their promising antimicrobial activities. The inhibitory activity of compound 7d was found to be higher than that of 2. Molecular docking work suggests that compound 7d might bind at a pocket close to the ATPase ATP-binding domain.
|
Antibacterial activity against Bacillus subtilis at 25 ug/ml after overnight incubation by plate colony counting method relative to control
|
Bacillus subtilis
|
85.0
%
|
|
Journal : Eur J Med Chem
Title : Design, synthesis and antimicrobial activities of thiouracil derivatives containing triazolo-thiadiazole as SecA inhibitors.
Year : 2017
Volume : 127
First Page : 159
Last Page : 165
Authors : Cui P, Li X, Zhu M, Wang B, Liu J, Chen H.
Abstract : A series of novel thiouracil derivatives containing a triazolo-thiadiazole moiety (7a-7l) have been synthesized by structural modifications on a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7d and 7g were also tested for their inhibitory activities against SecA ATPase due to their promising antimicrobial activities. The inhibitory activity of compound 7d was found to be higher than that of 2. Molecular docking work suggests that compound 7d might bind at a pocket close to the ATPase ATP-binding domain.
|
Antibacterial activity against Bacillus amyloliquefaciens at 25 ug/ml after 24 hrs by plate colony counting method relative to control
|
Bacillus amyloliquefaciens
|
84.0
%
|
|
Journal : Bioorg Med Chem Lett
Title : Design, synthesis and antibacterial activities of thiouracil derivatives containing acyl thiourea as SecA inhibitors.
Year : 2017
Volume : 27
Issue : 10
First Page : 2234
Last Page : 2237
Authors : Cui P, Li X, Zhu M, Wang B, Liu J, Chen H.
Abstract : A series of novel thiouracil derivatives containing an acyl thiourea moiety (7a-7x) have been synthesized by structural modification of a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7c, 7m, 7u, 7v exhibited promising activities against above bacteria. Such four compounds were further tested for their inhibitory activity against SecA ATPase, and the results showed that compounds 7c and 7u had higher inhibitory activities than that of compound 2. Molecular docking work suggests that compound 7u might bind at a pocket close to the ATPase ATP-binding domain.
|
Antibacterial activity against Staphylococcus aureus at 25 ug/ml after 24 hrs by plate colony counting method relative to control
|
Staphylococcus aureus
|
78.0
%
|
|
Journal : Bioorg Med Chem Lett
Title : Design, synthesis and antibacterial activities of thiouracil derivatives containing acyl thiourea as SecA inhibitors.
Year : 2017
Volume : 27
Issue : 10
First Page : 2234
Last Page : 2237
Authors : Cui P, Li X, Zhu M, Wang B, Liu J, Chen H.
Abstract : A series of novel thiouracil derivatives containing an acyl thiourea moiety (7a-7x) have been synthesized by structural modification of a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7c, 7m, 7u, 7v exhibited promising activities against above bacteria. Such four compounds were further tested for their inhibitory activity against SecA ATPase, and the results showed that compounds 7c and 7u had higher inhibitory activities than that of compound 2. Molecular docking work suggests that compound 7u might bind at a pocket close to the ATPase ATP-binding domain.
|
Antibacterial activity against Bacillus subtilis at 25 ug/ml after 24 hrs by plate colony counting method relative to control
|
Bacillus subtilis
|
89.0
%
|
|
Journal : Bioorg Med Chem Lett
Title : Design, synthesis and antibacterial activities of thiouracil derivatives containing acyl thiourea as SecA inhibitors.
Year : 2017
Volume : 27
Issue : 10
First Page : 2234
Last Page : 2237
Authors : Cui P, Li X, Zhu M, Wang B, Liu J, Chen H.
Abstract : A series of novel thiouracil derivatives containing an acyl thiourea moiety (7a-7x) have been synthesized by structural modification of a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7c, 7m, 7u, 7v exhibited promising activities against above bacteria. Such four compounds were further tested for their inhibitory activity against SecA ATPase, and the results showed that compounds 7c and 7u had higher inhibitory activities than that of compound 2. Molecular docking work suggests that compound 7u might bind at a pocket close to the ATPase ATP-binding domain.
|
Antibacterial activity against Bacillus subtilis MTCC 441 by broth microdilution method
|
Bacillus subtilis
|
100.0
ug.mL-1
|
|
Journal : Bioorg Med Chem
Title : Recently reported biological activities of pyrazole compounds.
Year : 2017
Volume : 25
Issue : 21
First Page : 5891
Last Page : 5903
Authors : Faria JV, Vegi PF, Miguita AGC, Dos Santos MS, Boechat N, Bernardino AMR.
Abstract : The pyrazole nucleus is an aromatic azole heterocycle with two adjacent nitrogen atoms. Pyrazole derivatives have exhibited a broad spectrum of biological activities, and approved pyrazole-containing drugs include celecoxib, antipyrine, phenylbutazone, rimonabant, and dipyrone. Many research groups have synthesized and evaluated pyrazoles against several biological agents. This review examines recent publications relating the structures of pyrazoles with their corresponding biological activities.
|
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
|
6.88
%
|
|
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.
|
Antibacterial activity against Escherichia coli ATCC 8739 incubated for 24 hrs by resazurin dye based fluorimetric assay
|
Escherichia coli
|
250.0
nM
|
|
Journal : Eur J Med Chem
Title : The synthesis and in vitro biological evaluation of novel fluorinated tetrahydrobenzo[j]phenanthridine-7,12-diones against Mycobacterium tuberculosis.
Year : 2019
Volume : 181
First Page : 111549
Last Page : 111549
Authors : Cappoen D, Torfs E, Meiresonne T, Claes P, Semina E, Holvoet F, de Macedo MB, Cools F, Piller T, Matheeussen A, Van Calster K, Caljon G, Delputte P, Maes L, Neyrolles O, De Kimpe N, Mangelinckx S, Cos P.
Abstract : Tuberculosis (TB) still has a major impact on public health. In order to efficiently eradicate this life-threatening disease, the exploration of novel anti-TB drugs is of paramount importance. As part of our program to design new 2-azaanthraquinones with anti-mycobacterial activity, various "out-of-plane" tetrahydro- and octahydrobenzo[j]phenanthridinediones were synthesized. In this study, the scaffold of the most promising hits was further optimized in an attempt to improve the bioactivity and to decrease enzymatic degradation. The rudiment bio-evaluation of a small library of fluorinated tetrahydrobenzo[j]phenanthridine-7,12-dione derivatives indicated no significant improvement of the bio-activity against intracellular and extracellular Mycobacterium tuberculosis (Mtb). Though, the derivatives showed an acceptable toxicity against J774A.1 macrophages and early signs of genotoxicity were absent. All derivatives showed to be metabolic stabile in the presence of both phase I and phase II murine or human microsomes. Finally, the onset of reactive oxygen species within Mtb after exposure to the derivatives was measured by electron paramagnetic resonance (EPR). Results showed that the most promising fluorinated derivative is still a possible candidate for the subversive inhibition of mycothione reductase.
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 9027 incubated for 24 hrs by resazurin dye based fluorimetric assay
|
Pseudomonas aeruginosa
|
500.0
nM
|
|
Journal : Eur J Med Chem
Title : The synthesis and in vitro biological evaluation of novel fluorinated tetrahydrobenzo[j]phenanthridine-7,12-diones against Mycobacterium tuberculosis.
Year : 2019
Volume : 181
First Page : 111549
Last Page : 111549
Authors : Cappoen D, Torfs E, Meiresonne T, Claes P, Semina E, Holvoet F, de Macedo MB, Cools F, Piller T, Matheeussen A, Van Calster K, Caljon G, Delputte P, Maes L, Neyrolles O, De Kimpe N, Mangelinckx S, Cos P.
Abstract : Tuberculosis (TB) still has a major impact on public health. In order to efficiently eradicate this life-threatening disease, the exploration of novel anti-TB drugs is of paramount importance. As part of our program to design new 2-azaanthraquinones with anti-mycobacterial activity, various "out-of-plane" tetrahydro- and octahydrobenzo[j]phenanthridinediones were synthesized. In this study, the scaffold of the most promising hits was further optimized in an attempt to improve the bioactivity and to decrease enzymatic degradation. The rudiment bio-evaluation of a small library of fluorinated tetrahydrobenzo[j]phenanthridine-7,12-dione derivatives indicated no significant improvement of the bio-activity against intracellular and extracellular Mycobacterium tuberculosis (Mtb). Though, the derivatives showed an acceptable toxicity against J774A.1 macrophages and early signs of genotoxicity were absent. All derivatives showed to be metabolic stabile in the presence of both phase I and phase II murine or human microsomes. Finally, the onset of reactive oxygen species within Mtb after exposure to the derivatives was measured by electron paramagnetic resonance (EPR). Results showed that the most promising fluorinated derivative is still a possible candidate for the subversive inhibition of mycothione reductase.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
34.2
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
21.69
%
|
|
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
|
-0.15
%
|
|
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
|
-0.08
%
|
|
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
|
-0.15
%
|
|
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
|
-0.08
%
|
|
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.
|
Antiproliferative activity against human A549 cells after 72 hrs by MTT assay
|
Homo sapiens
|
302.0
nM
|
|
Journal : Eur J Med Chem
Title : Quinolone hybrids and their anti-cancer activities: An overview.
Year : 2019
Volume : 165
First Page : 59
Last Page : 79
Authors : Gao F, Zhang X, Wang T, Xiao J.
Abstract : The global pandemic of drug-sensitive cancers and the increasing threat from drug-resistant cancers make an urgent need to develop more effective anti-cancer candidates. Quinolone derivatives possess promising anti-cancer activity, and some of them have already been approved to treat cancers or under clinical trials. Hybridization of quinolone with other anti-cancer pharmacophores may provide more efficient anti-cancer candidates, so quinolone hybrids worth to be investigated. In this review, the recent advances in the development of novel quinolone hybrids as potential anti-cancer agents are highlighted, and the structure-activity relationship is also discussed to provide an insight for further development of more active quinolone hybrids.
|
Antiproliferative activity against human HL60 cells after 72 hrs by MTT assay
|
Homo sapiens
|
302.0
nM
|
|
Journal : Eur J Med Chem
Title : Quinolone hybrids and their anti-cancer activities: An overview.
Year : 2019
Volume : 165
First Page : 59
Last Page : 79
Authors : Gao F, Zhang X, Wang T, Xiao J.
Abstract : The global pandemic of drug-sensitive cancers and the increasing threat from drug-resistant cancers make an urgent need to develop more effective anti-cancer candidates. Quinolone derivatives possess promising anti-cancer activity, and some of them have already been approved to treat cancers or under clinical trials. Hybridization of quinolone with other anti-cancer pharmacophores may provide more efficient anti-cancer candidates, so quinolone hybrids worth to be investigated. In this review, the recent advances in the development of novel quinolone hybrids as potential anti-cancer agents are highlighted, and the structure-activity relationship is also discussed to provide an insight for further development of more active quinolone hybrids.
