title: Synthesis and in vitro evaluation of novel highly potent coumarin inhibitors of gyrase B.
abstract: 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.
authors.affiliation: Medicinal Chemistry, Infectious Disease, Romainville, France.
authors.forename: P
authors.initials: P
authors.lastname: Laurin
authors.forename: D
authors.initials: D
authors.lastname: Ferroud
authors.forename: M
authors.initials: M
authors.lastname: Klich
authors.forename: C
authors.initials: C
authors.lastname: Dupuis-Hamelin
authors.forename: P
authors.initials: P
authors.lastname: Mauvais
authors.forename: P
authors.initials: P
authors.lastname: Lassaigne
authors.forename: A
authors.initials: A
authors.lastname: Bonnefoy
authors.forename: B
authors.initials: B
authors.lastname: Musicki
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D003374:Coumarins; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; C006260:clorobiocin; D027081:DNA Gyrase