2-Phenyl-5,6-dihydro-2H-thieno[3,2-c]pyrazol-3-ol derivatives as new inhibitors of bacterial cell wall biosynthesis.
Twenty-five 2-phenyl-5,6-dihydro-2H-thieno[3,2-c]pyrazol-3-ol derivatives were synthesized for evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them demonstrated good inhibitory activity against Staphylococcus aureus MurB, MurC and MurD enzymes in vitro and antimicrobial activity against gram-positive bacteria including MRSA, VRE and PRSP. However, when they were tested in the presence of 4% bovine serum albumin, the MIC values increased to greater than 128 microg/mL against PRSP. None of the compounds demonstrated activity against gram-negative bacteria at MIC <32 microg/mL.
Li
Zhong
Z
Chemical Sciences and Infectious Diseases, Wyeth Research, Pearl River, NY 10965, USA.
Francisco
Gerardo D
GD
Hu
William
W
Labthavikul
Pornpen
P
Petersen
Peter J
PJ
Severin
Anatoly
A
Singh
Guy
G
Yang
Youjun
Y
Rasmussen
Beth A
BA
Lin
Yang-I
YI
Skotnicki
Jerauld S
JS
Mansour
Tarek S
TS
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D000900:Anti-Bacterial Agents