Synthesis and in vitro evaluation of novel highly potent coumarin inhibitors of gyrase B.
The design, synthesis, and in vitro biological activity of a series of novel coumarin inhibitors of gyrase B is presented. Replacement of the 3-acylamino residue (3-NHCOR) of coumarin drugs with reversed isosteres C(=O)R, C(=N-OR)R', COOR, CONHR and CONHOR leads to highly potent analogues which displayed excellent inhibition of the negative supercoiling of the relaxed DNA and antibacterial activity.
Laurin
P
P
Medicinal Chemistry, Infectious Disease, Romainville, France.
Ferroud
D
D
Klich
M
M
Dupuis-Hamelin
C
C
Mauvais
P
P
Lassaigne
P
P
Bonnefoy
A
A
Musicki
B
B
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D027081:DNA Gyrase; D015195:Drug Design; D016983:Enterococcus / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D020128:Inhibitory Concentration 50; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009675:Novobiocin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D013210:Staphylococcus / Q000187:drug effects; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D003374:Coumarins; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; C006260:clorobiocin; D027081:DNA Gyrase