Synthesis and biological evaluation of coumarincarboxylic acids as inhibitors of gyrase B. L-rhamnose as an effective substitute for L-noviose.
A series of novobiocin-like coumarincarboxylic acids has been prepared bearing the L-rhamnosyl moiety as the sugar portion of the molecule. The similar DNA gyrase inhibitory activity of the novel class of coumarins to that of novobiocin demonstrates that L-rhamnose can effectively replace L-noviose. Introduction of alkyl side-chains at C-5 of coumarin leads to improved in vitro antibacterial properties in the novel series.
Ferroud
D
D
Medicinal Chemistry, Hoechst Marion Roussel, Romainville, France.
Collard
J
J
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; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D027081:DNA Gyrase; D004278:DNA, Superhelical / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D015394:Molecular Structure; D009675:Novobiocin / Q000031:analogs & derivatives / Q000494:pharmacology; D012210:Rhamnose / Q000031:analogs & derivatives; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D003374:Coumarins; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; C006260:clorobiocin; D027081:DNA Gyrase; D012210:Rhamnose