|
Antimicrobial activity against methicillin-susceptible Staphylococcus aureus ATCC 25923 after phagocytosis by human THP1 macrophages assessed as reduction in bacterial count after 24 hrs
|
Staphylococcus aureus
|
0.14
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Role of acidic pH in the susceptibility of intraphagocytic methicillin-resistant Staphylococcus aureus strains to meropenem and cloxacillin.
Year : 2007
Volume : 51
Issue : 5
First Page : 1627
Last Page : 1632
Authors : Lemaire S, Van Bambeke F, Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM.
Abstract : Early studies showed that methicillin-resistant Staphylococcus aureus (MRSA) strains are susceptible to beta-lactams when they are exposed to pH < or = 5.5 in broth. Because S. aureus survives in the phagolysosomes of macrophages, where the pH may be acidic, we have examined the susceptibility of MRSA ATCC 33591 phagocytized by human THP-1 macrophages to meropenem (MEM) and cloxacillin (CLX). Using a pharmacodynamic model assessing key pharmacological (50% effective concentration and maximal efficacy) and microbiological (static concentration) descriptors of antibiotic activity, we show that intraphagocytic MRSA strains are as sensitive to MEM and CLX as methicillin-susceptible S. aureus (MSSA; ATCC 25923). This observation was replicated in broth if the pH was brought to 5.5 and was confirmed with clinical strains. Electron microscopy showed that both the MRSA and the MSSA strains localized and multiplied in membrane-bounded structures (phagolysosomes) in the absence of beta-lactams. Incubation of the infected macrophages with ammonium chloride (to raise the phagolysosomal pH) made MRSA insensitive to MEM and CLX. No difference was seen in mec, mecA, mecI, mecR1, femA, and femB expression (reversed transcription-PCR) or in PBP 2a content (immunodetection) in MRSA grown in broth at pH 5.5 compared with that in MRSA grown in broth at 7.4. The level of [(14)C]benzylpenicillin binding to cell walls prepared from a non-beta-lactamase-producing MRSA clinical isolate was two times lower than that to cell walls prepared from MSSA ATCC 25923 at pH 7.4, but the levels increased to similar values for both strains at pH 5.5. These data suggest that the restoration of susceptibility of intraphagocytic of MRSA to MEM and CLX is due to the acidic pH prevailing in phagolysosomes and is mediated by an enhanced binding to penicillin-binding proteins.
|
Antimicrobial activity against methicillin-resistant Staphylococcus aureus ATCC 25923 after phagocytosis by human THP1 macrophages assessed as reduction in bacterial count after 24 hrs
|
Staphylococcus aureus
|
0.16
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Role of acidic pH in the susceptibility of intraphagocytic methicillin-resistant Staphylococcus aureus strains to meropenem and cloxacillin.
Year : 2007
Volume : 51
Issue : 5
First Page : 1627
Last Page : 1632
Authors : Lemaire S, Van Bambeke F, Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM.
Abstract : Early studies showed that methicillin-resistant Staphylococcus aureus (MRSA) strains are susceptible to beta-lactams when they are exposed to pH < or = 5.5 in broth. Because S. aureus survives in the phagolysosomes of macrophages, where the pH may be acidic, we have examined the susceptibility of MRSA ATCC 33591 phagocytized by human THP-1 macrophages to meropenem (MEM) and cloxacillin (CLX). Using a pharmacodynamic model assessing key pharmacological (50% effective concentration and maximal efficacy) and microbiological (static concentration) descriptors of antibiotic activity, we show that intraphagocytic MRSA strains are as sensitive to MEM and CLX as methicillin-susceptible S. aureus (MSSA; ATCC 25923). This observation was replicated in broth if the pH was brought to 5.5 and was confirmed with clinical strains. Electron microscopy showed that both the MRSA and the MSSA strains localized and multiplied in membrane-bounded structures (phagolysosomes) in the absence of beta-lactams. Incubation of the infected macrophages with ammonium chloride (to raise the phagolysosomal pH) made MRSA insensitive to MEM and CLX. No difference was seen in mec, mecA, mecI, mecR1, femA, and femB expression (reversed transcription-PCR) or in PBP 2a content (immunodetection) in MRSA grown in broth at pH 5.5 compared with that in MRSA grown in broth at 7.4. The level of [(14)C]benzylpenicillin binding to cell walls prepared from a non-beta-lactamase-producing MRSA clinical isolate was two times lower than that to cell walls prepared from MSSA ATCC 25923 at pH 7.4, but the levels increased to similar values for both strains at pH 5.5. These data suggest that the restoration of susceptibility of intraphagocytic of MRSA to MEM and CLX is due to the acidic pH prevailing in phagolysosomes and is mediated by an enhanced binding to penicillin-binding proteins.
|
Antimicrobial activity against methicillin-susceptible Staphylococcus aureus ATCC 25923 after phagocytosis by human THP1 macrophages assessed as reduction in bacterial count at pH 7.4 after 24 hrs
|
Staphylococcus aureus
|
0.29
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Role of acidic pH in the susceptibility of intraphagocytic methicillin-resistant Staphylococcus aureus strains to meropenem and cloxacillin.
Year : 2007
Volume : 51
Issue : 5
First Page : 1627
Last Page : 1632
Authors : Lemaire S, Van Bambeke F, Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM.
Abstract : Early studies showed that methicillin-resistant Staphylococcus aureus (MRSA) strains are susceptible to beta-lactams when they are exposed to pH < or = 5.5 in broth. Because S. aureus survives in the phagolysosomes of macrophages, where the pH may be acidic, we have examined the susceptibility of MRSA ATCC 33591 phagocytized by human THP-1 macrophages to meropenem (MEM) and cloxacillin (CLX). Using a pharmacodynamic model assessing key pharmacological (50% effective concentration and maximal efficacy) and microbiological (static concentration) descriptors of antibiotic activity, we show that intraphagocytic MRSA strains are as sensitive to MEM and CLX as methicillin-susceptible S. aureus (MSSA; ATCC 25923). This observation was replicated in broth if the pH was brought to 5.5 and was confirmed with clinical strains. Electron microscopy showed that both the MRSA and the MSSA strains localized and multiplied in membrane-bounded structures (phagolysosomes) in the absence of beta-lactams. Incubation of the infected macrophages with ammonium chloride (to raise the phagolysosomal pH) made MRSA insensitive to MEM and CLX. No difference was seen in mec, mecA, mecI, mecR1, femA, and femB expression (reversed transcription-PCR) or in PBP 2a content (immunodetection) in MRSA grown in broth at pH 5.5 compared with that in MRSA grown in broth at 7.4. The level of [(14)C]benzylpenicillin binding to cell walls prepared from a non-beta-lactamase-producing MRSA clinical isolate was two times lower than that to cell walls prepared from MSSA ATCC 25923 at pH 7.4, but the levels increased to similar values for both strains at pH 5.5. These data suggest that the restoration of susceptibility of intraphagocytic of MRSA to MEM and CLX is due to the acidic pH prevailing in phagolysosomes and is mediated by an enhanced binding to penicillin-binding proteins.
|
Antimicrobial activity against methicillin-susceptible Staphylococcus aureus ATCC 25923 after phagocytosis by human THP1 macrophages assessed as reduction in bacterial count at pH 5.5 after 24 hrs
|
Staphylococcus aureus
|
0.2
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Role of acidic pH in the susceptibility of intraphagocytic methicillin-resistant Staphylococcus aureus strains to meropenem and cloxacillin.
Year : 2007
Volume : 51
Issue : 5
First Page : 1627
Last Page : 1632
Authors : Lemaire S, Van Bambeke F, Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM.
Abstract : Early studies showed that methicillin-resistant Staphylococcus aureus (MRSA) strains are susceptible to beta-lactams when they are exposed to pH < or = 5.5 in broth. Because S. aureus survives in the phagolysosomes of macrophages, where the pH may be acidic, we have examined the susceptibility of MRSA ATCC 33591 phagocytized by human THP-1 macrophages to meropenem (MEM) and cloxacillin (CLX). Using a pharmacodynamic model assessing key pharmacological (50% effective concentration and maximal efficacy) and microbiological (static concentration) descriptors of antibiotic activity, we show that intraphagocytic MRSA strains are as sensitive to MEM and CLX as methicillin-susceptible S. aureus (MSSA; ATCC 25923). This observation was replicated in broth if the pH was brought to 5.5 and was confirmed with clinical strains. Electron microscopy showed that both the MRSA and the MSSA strains localized and multiplied in membrane-bounded structures (phagolysosomes) in the absence of beta-lactams. Incubation of the infected macrophages with ammonium chloride (to raise the phagolysosomal pH) made MRSA insensitive to MEM and CLX. No difference was seen in mec, mecA, mecI, mecR1, femA, and femB expression (reversed transcription-PCR) or in PBP 2a content (immunodetection) in MRSA grown in broth at pH 5.5 compared with that in MRSA grown in broth at 7.4. The level of [(14)C]benzylpenicillin binding to cell walls prepared from a non-beta-lactamase-producing MRSA clinical isolate was two times lower than that to cell walls prepared from MSSA ATCC 25923 at pH 7.4, but the levels increased to similar values for both strains at pH 5.5. These data suggest that the restoration of susceptibility of intraphagocytic of MRSA to MEM and CLX is due to the acidic pH prevailing in phagolysosomes and is mediated by an enhanced binding to penicillin-binding proteins.
|
Antimicrobial activity against methicillin-susceptible Staphylococcus aureus ATCC 25923 after phagocytosis by human THP1 macrophages assessed as reduction in bacterial count at pH 5.5 after 24 hrs
|
Staphylococcus aureus
|
0.33
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Role of acidic pH in the susceptibility of intraphagocytic methicillin-resistant Staphylococcus aureus strains to meropenem and cloxacillin.
Year : 2007
Volume : 51
Issue : 5
First Page : 1627
Last Page : 1632
Authors : Lemaire S, Van Bambeke F, Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM.
Abstract : Early studies showed that methicillin-resistant Staphylococcus aureus (MRSA) strains are susceptible to beta-lactams when they are exposed to pH < or = 5.5 in broth. Because S. aureus survives in the phagolysosomes of macrophages, where the pH may be acidic, we have examined the susceptibility of MRSA ATCC 33591 phagocytized by human THP-1 macrophages to meropenem (MEM) and cloxacillin (CLX). Using a pharmacodynamic model assessing key pharmacological (50% effective concentration and maximal efficacy) and microbiological (static concentration) descriptors of antibiotic activity, we show that intraphagocytic MRSA strains are as sensitive to MEM and CLX as methicillin-susceptible S. aureus (MSSA; ATCC 25923). This observation was replicated in broth if the pH was brought to 5.5 and was confirmed with clinical strains. Electron microscopy showed that both the MRSA and the MSSA strains localized and multiplied in membrane-bounded structures (phagolysosomes) in the absence of beta-lactams. Incubation of the infected macrophages with ammonium chloride (to raise the phagolysosomal pH) made MRSA insensitive to MEM and CLX. No difference was seen in mec, mecA, mecI, mecR1, femA, and femB expression (reversed transcription-PCR) or in PBP 2a content (immunodetection) in MRSA grown in broth at pH 5.5 compared with that in MRSA grown in broth at 7.4. The level of [(14)C]benzylpenicillin binding to cell walls prepared from a non-beta-lactamase-producing MRSA clinical isolate was two times lower than that to cell walls prepared from MSSA ATCC 25923 at pH 7.4, but the levels increased to similar values for both strains at pH 5.5. These data suggest that the restoration of susceptibility of intraphagocytic of MRSA to MEM and CLX is due to the acidic pH prevailing in phagolysosomes and is mediated by an enhanced binding to penicillin-binding proteins.
|
Inhibition of Bocillin FL binding to PBP1A in Escherichia coli MC4100 membranes
|
Escherichia coli
|
1.7
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP1B in Escherichia coli MC4100 membranes
|
Escherichia coli
|
1.3
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP2 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
0.008
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP3 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
0.6
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP4 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
0.02
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP5 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP6 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
0.03
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP1A in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
0.5
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP1B in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
0.5
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP2 in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
0.05
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP3 in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
0.08
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP4 in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
0.008
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP5/6 in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
16.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP1A in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
0.6
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP1B in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
0.6
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP2 in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
0.06
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP3 in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
0.08
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP4 in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
0.02
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Inhibition of Bocillin FL binding to PBP5/6 in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
Abstract : Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
|
Binding affinity to PBP2a in methicillin-resistant Staphylococcus aureus 123-1 by [14C]benzylpenicillin labelled competitive assay
|
Staphylococcus aureus
|
130.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Potent in vitro activity of tomopenem (CS-023) against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 8
First Page : 2849
Last Page : 2854
Authors : Koga T, Masuda N, Kakuta M, Namba E, Sugihara C, Fukuoka T.
Abstract : Tomopenem (formerly CS-023) is a novel 1beta-methylcarbapenem with broad-spectrum coverage of gram-positive and gram-negative pathogens. Its antibacterial activity against European clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa was compared with those of imipenem and meropenem. The MICs of tomopenem against MRSA and P. aeruginosa at which 90% of the isolates tested were inhibited were 8 and 4 microg/ml, respectively, and were equal to or more than fourfold lower than those of imipenem and meropenem. The antibacterial activity of tomopenem against MRSA was correlated with a higher affinity for the penicillin-binding protein (PBP) 2a. Its activity against laboratory mutants of P. aeruginosa with (i) overproduction of chromosomally coded AmpC beta-lactamase; (ii) overproduction of the multidrug efflux pumps MexAB-OprM, MexCD-OprJ, and MexEF-OprN; (iii) deficiency in OprD; and (iv) various combinations of AmpC overproduction, MexAB-OprM overproduction, and OprD deficiency were tested. The increases in the MIC of tomopenem against each single mutant compared with that against its parent strain were within a fourfold range. Tomopenem exhibited antibacterial activity against all mutants, with an observed MIC range of 0.5 to 8 microg/ml. These results suggest that the antibacterial activity of tomopenem against the clinical isolates of MRSA and P. aeruginosa should be ascribed to its high affinity for PBP 2a and its activity against the mutants of P. aeruginosa, respectively.
|
Binding affinity to PBP2a in methicillin-resistant Staphylococcus aureus 12386-1 by [14C]benzylpenicillin labelled competitive assay
|
Staphylococcus aureus
|
53.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Potent in vitro activity of tomopenem (CS-023) against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 8
First Page : 2849
Last Page : 2854
Authors : Koga T, Masuda N, Kakuta M, Namba E, Sugihara C, Fukuoka T.
Abstract : Tomopenem (formerly CS-023) is a novel 1beta-methylcarbapenem with broad-spectrum coverage of gram-positive and gram-negative pathogens. Its antibacterial activity against European clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa was compared with those of imipenem and meropenem. The MICs of tomopenem against MRSA and P. aeruginosa at which 90% of the isolates tested were inhibited were 8 and 4 microg/ml, respectively, and were equal to or more than fourfold lower than those of imipenem and meropenem. The antibacterial activity of tomopenem against MRSA was correlated with a higher affinity for the penicillin-binding protein (PBP) 2a. Its activity against laboratory mutants of P. aeruginosa with (i) overproduction of chromosomally coded AmpC beta-lactamase; (ii) overproduction of the multidrug efflux pumps MexAB-OprM, MexCD-OprJ, and MexEF-OprN; (iii) deficiency in OprD; and (iv) various combinations of AmpC overproduction, MexAB-OprM overproduction, and OprD deficiency were tested. The increases in the MIC of tomopenem against each single mutant compared with that against its parent strain were within a fourfold range. Tomopenem exhibited antibacterial activity against all mutants, with an observed MIC range of 0.5 to 8 microg/ml. These results suggest that the antibacterial activity of tomopenem against the clinical isolates of MRSA and P. aeruginosa should be ascribed to its high affinity for PBP 2a and its activity against the mutants of P. aeruginosa, respectively.
|
PUBCHEM_BIOASSAY: Luminescence Microorganism-Based Dose Confirmation HTS to Identify Compounds Cytotoxic to SK(-)GAS Group A Streptococcus. (Class of assay: confirmatory) [Related pubchem assays: 1677 (Project Summary), 1662 (Primary HTS)]
|
Streptococcus
|
153.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Luminescence Microorganism-Based Dose Confirmation HTS to Identify Inhibitors of Streptokinase Promotor Activity. (Class of assay: confirmatory) [Related pubchem assays: 1677 (Project Summary), 1662 (Primary HTS)]
|
Streptococcus pyogenes M1 GAS
|
127.0
nM
|
|
Title : PubChem BioAssay data set
|
Antibacterial activity against Staphylococcus aureus ATCC 6538P by microdilution method
|
Staphylococcus aureus
|
0.06
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Antibacterial activity against Escherichia coli NIHJ by microdilution method
|
Escherichia coli
|
0.03
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 15692 by microdilution method
|
Pseudomonas aeruginosa
|
1.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP1 in Staphylococcus aureus ATCC 6538P
|
Staphylococcus aureus
|
0.044
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP2 Staphylococcus aureus ATCC 6538P
|
Staphylococcus aureus
|
0.26
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP3 in Staphylococcus aureus ATCC 6538P
|
Staphylococcus aureus
|
130.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP4 in Staphylococcus aureus ATCC 6538P
|
Staphylococcus aureus
|
0.071
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP1A in Escherichia coli NIHJ
|
Escherichia coli
|
0.82
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP1B in Escherichia coli NIHJ
|
Escherichia coli
|
0.77
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP2 in Escherichia coli NIHJ
|
Escherichia coli
|
0.016
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP3 in Escherichia coli NIHJ
|
Escherichia coli
|
0.39
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP4 in Escherichia coli NIHJ
|
Escherichia coli
|
0.047
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP5 in Escherichia coli NIHJ
|
Escherichia coli
|
1.2
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP6 Escherichia coli NIHJ
|
Escherichia coli
|
15.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP1A in Pseudomonas aeruginosa ATCC 15692
|
Pseudomonas aeruginosa
|
0.12
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP1B in Pseudomonas aeruginosa ATCC 15692
|
Pseudomonas aeruginosa
|
0.11
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP2 in Pseudomonas aeruginosa ATCC 15692
|
Pseudomonas aeruginosa
|
0.018
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP3 in Pseudomonas aeruginosa ATCC 15692
|
Pseudomonas aeruginosa
|
0.013
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP4 in Pseudomonas aeruginosa ATCC 15692
|
Pseudomonas aeruginosa
|
0.0033
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP 5 in Pseudomonas aeruginosa ATCC 15692
|
Pseudomonas aeruginosa
|
4.5
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Displacement of [14C]benzylpenicillin from PBP 6 in Pseudomonas aeruginosa ATCC 15692
|
Pseudomonas aeruginosa
|
4.5
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Year : 2009
Volume : 53
Issue : 3
First Page : 1238
Last Page : 1241
Authors : Koga T, Sugihara C, Kakuta M, Masuda N, Namba E, Fukuoka T.
Abstract : Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.
|
Binding affinity to native signal deficient and TEV cleavage site containing His-tagged Klebsiella pneumoniae OXA-48 expressed in Escherichia coli assessed as dissociation rate constant by SPR assay
|
Klebsiella pneumoniae
|
0.3463
/s
|
|
Journal : J Med Chem
Title : Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening.
Year : 2016
Volume : 59
Issue : 11
First Page : 5542
Last Page : 5554
Authors : Lund BA, Christopeit T, Guttormsen Y, Bayer A, Leiros HK.
Abstract : The spread of antibiotic resistant bacteria is a global threat that shakes the foundations of modern healthcare. β-Lactamases are enzymes that confer resistance to β-lactam antibiotics in bacteria, and there is a critical need for new inhibitors of these enzymes for combination therapy together with an antibiotic. With this in mind, we have screened a library of 490 fragments to identify starting points for the development of new inhibitors of the class D β-lactamase oxacillinase-48 (OXA-48) through surface plasmon resonance (SPR), dose-rate inhibition assays, and X-ray crystallography. Furthermore, we have uncovered structure-activity relationships and used alternate conformations from a crystallographic structure to grow a fragment into a more potent compound with a KD of 50 μM and an IC50 of 18 μM.
|
Binding affinity to native signal deficient and TEV cleavage site containing His-tagged Klebsiella pneumoniae OXA-48 expressed in Escherichia coli assessed as dissociation constant by SPR assay
|
Klebsiella pneumoniae
|
850.0
nM
|
|
Journal : J Med Chem
Title : Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening.
Year : 2016
Volume : 59
Issue : 11
First Page : 5542
Last Page : 5554
Authors : Lund BA, Christopeit T, Guttormsen Y, Bayer A, Leiros HK.
Abstract : The spread of antibiotic resistant bacteria is a global threat that shakes the foundations of modern healthcare. β-Lactamases are enzymes that confer resistance to β-lactam antibiotics in bacteria, and there is a critical need for new inhibitors of these enzymes for combination therapy together with an antibiotic. With this in mind, we have screened a library of 490 fragments to identify starting points for the development of new inhibitors of the class D β-lactamase oxacillinase-48 (OXA-48) through surface plasmon resonance (SPR), dose-rate inhibition assays, and X-ray crystallography. Furthermore, we have uncovered structure-activity relationships and used alternate conformations from a crystallographic structure to grow a fragment into a more potent compound with a KD of 50 μM and an IC50 of 18 μM.
|
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600)
|
Staphylococcus aureus subsp. aureus
|
-14.17
%
|
|
|
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
|
Escherichia coli
|
7.87
%
|
|
|
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
0.03
%
|
|
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
8.16
%
|
|
|
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
|
Acinetobacter baumannii
|
10.36
%
|
|
|
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
|
3.42
%
|
|
|
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570)
|
Cryptococcus neoformans
|
2.76
%
|
|
|
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
|
10.13
%
|
|
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.
|
Antimicrobial activity against Candida albicans ATCC 90028 assessed as inhibition of microbial growth by CLSI based method
|
Candida albicans
|
300.0
nM
|
|
Journal : J Nat Prod
Title : Anthraquinone-Based Specialized Metabolites from Rhizomes of <i>Bulbine natalensis</i>.
Year : 2019
Volume : 82
Issue : 7
First Page : 1893
Last Page : 1901
Authors : Bae JY, Ali Z, Wang YH, Chittiboyina AG, Zaki AA, Viljoen AM, Khan IA.
Abstract : The rhizomes of <i>Bulbine natalensis</i> furnished six previously unreported anthraquinone derivatives (<b>1</b>-<b>6</b>), together with eight known specialized metabolites. Their structures were determined by interpretation of 1D and 2D NMR and HRESIMS data. The absolute configurations of compounds <b>1</b>-<b>6</b> were determined by specific rotation and circular dichroism experiments. The isolated compounds were evaluated for antimicrobial activities, and compound <b>1</b> was found to be a moderate inhibitor (IC<sub>50</sub> 0.02 μM) against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).
|
Antimicrobial activity against Aspergillus fumigatus ATCC 90906 assessed as inhibition of microbial growth by CLSI based method
|
Aspergillus fumigatus
|
300.0
nM
|
|
Journal : J Nat Prod
Title : Anthraquinone-Based Specialized Metabolites from Rhizomes of <i>Bulbine natalensis</i>.
Year : 2019
Volume : 82
Issue : 7
First Page : 1893
Last Page : 1901
Authors : Bae JY, Ali Z, Wang YH, Chittiboyina AG, Zaki AA, Viljoen AM, Khan IA.
Abstract : The rhizomes of <i>Bulbine natalensis</i> furnished six previously unreported anthraquinone derivatives (<b>1</b>-<b>6</b>), together with eight known specialized metabolites. Their structures were determined by interpretation of 1D and 2D NMR and HRESIMS data. The absolute configurations of compounds <b>1</b>-<b>6</b> were determined by specific rotation and circular dichroism experiments. The isolated compounds were evaluated for antimicrobial activities, and compound <b>1</b> was found to be a moderate inhibitor (IC<sub>50</sub> 0.02 μM) against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).
|
Antimicrobial activity against Cryptococcus neoformans ATCC 90113 assessed as inhibition of microbial growth by CLSI based method
|
Cryptococcus neoformans
|
300.0
nM
|
|
Journal : J Nat Prod
Title : Anthraquinone-Based Specialized Metabolites from Rhizomes of <i>Bulbine natalensis</i>.
Year : 2019
Volume : 82
Issue : 7
First Page : 1893
Last Page : 1901
Authors : Bae JY, Ali Z, Wang YH, Chittiboyina AG, Zaki AA, Viljoen AM, Khan IA.
Abstract : The rhizomes of <i>Bulbine natalensis</i> furnished six previously unreported anthraquinone derivatives (<b>1</b>-<b>6</b>), together with eight known specialized metabolites. Their structures were determined by interpretation of 1D and 2D NMR and HRESIMS data. The absolute configurations of compounds <b>1</b>-<b>6</b> were determined by specific rotation and circular dichroism experiments. The isolated compounds were evaluated for antimicrobial activities, and compound <b>1</b> was found to be a moderate inhibitor (IC<sub>50</sub> 0.02 μM) against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).
|
Antimicrobial activity against methicillin-resistant Staphylococcus aureus ATCC 43300 assessed as inhibition of microbial growth by CLSI based method
|
Staphylococcus aureus
|
10.0
nM
|
|
Journal : J Nat Prod
Title : Anthraquinone-Based Specialized Metabolites from Rhizomes of <i>Bulbine natalensis</i>.
Year : 2019
Volume : 82
Issue : 7
First Page : 1893
Last Page : 1901
Authors : Bae JY, Ali Z, Wang YH, Chittiboyina AG, Zaki AA, Viljoen AM, Khan IA.
Abstract : The rhizomes of <i>Bulbine natalensis</i> furnished six previously unreported anthraquinone derivatives (<b>1</b>-<b>6</b>), together with eight known specialized metabolites. Their structures were determined by interpretation of 1D and 2D NMR and HRESIMS data. The absolute configurations of compounds <b>1</b>-<b>6</b> were determined by specific rotation and circular dichroism experiments. The isolated compounds were evaluated for antimicrobial activities, and compound <b>1</b> was found to be a moderate inhibitor (IC<sub>50</sub> 0.02 μM) against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).
|
Antimicrobial activity against Escherichia coli ATCC 35218 assessed as inhibition of microbial growth by CLSI based method
|
Escherichia coli
|
10.0
nM
|
|
Journal : J Nat Prod
Title : Anthraquinone-Based Specialized Metabolites from Rhizomes of <i>Bulbine natalensis</i>.
Year : 2019
Volume : 82
Issue : 7
First Page : 1893
Last Page : 1901
Authors : Bae JY, Ali Z, Wang YH, Chittiboyina AG, Zaki AA, Viljoen AM, Khan IA.
Abstract : The rhizomes of <i>Bulbine natalensis</i> furnished six previously unreported anthraquinone derivatives (<b>1</b>-<b>6</b>), together with eight known specialized metabolites. Their structures were determined by interpretation of 1D and 2D NMR and HRESIMS data. The absolute configurations of compounds <b>1</b>-<b>6</b> were determined by specific rotation and circular dichroism experiments. The isolated compounds were evaluated for antimicrobial activities, and compound <b>1</b> was found to be a moderate inhibitor (IC<sub>50</sub> 0.02 μM) against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).
|
Antimicrobial activity against Pseudomonas aeruginosa ATCC 27853 assessed as inhibition of microbial growth by CLSI based method
|
Pseudomonas aeruginosa
|
20.0
nM
|
|
Journal : J Nat Prod
Title : Anthraquinone-Based Specialized Metabolites from Rhizomes of <i>Bulbine natalensis</i>.
Year : 2019
Volume : 82
Issue : 7
First Page : 1893
Last Page : 1901
Authors : Bae JY, Ali Z, Wang YH, Chittiboyina AG, Zaki AA, Viljoen AM, Khan IA.
Abstract : The rhizomes of <i>Bulbine natalensis</i> furnished six previously unreported anthraquinone derivatives (<b>1</b>-<b>6</b>), together with eight known specialized metabolites. Their structures were determined by interpretation of 1D and 2D NMR and HRESIMS data. The absolute configurations of compounds <b>1</b>-<b>6</b> were determined by specific rotation and circular dichroism experiments. The isolated compounds were evaluated for antimicrobial activities, and compound <b>1</b> was found to be a moderate inhibitor (IC<sub>50</sub> 0.02 μM) against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
10.85
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
-4.064
%
|
|
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
|
-0.09
%
|
|
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
|
0.12
%
|
|
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
|
0.12
%
|
|
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
|
-0.09
%
|
|
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.
|
Inhibition of bacterial NDM-1 expressed in Escherichia coli BL21 (DE3) at 20 uM using meropenem as substrate incubated for 1 hr by spectrometry analysis relative to control
|
Bacteria
|
90.0
%
|
|
