Synthesis and characterization of a novel inhibitor of an aminoglycoside-inactivating enzyme.
A novel low-molecular weight inhibitor of an aminoglycoside-inactivating enzyme, initially isolated from fermentation broths of Streptomyces neyagawaensis, was determined to be 7-hydroxytropolone. Its structure was confirmed by synthesis. In vitro synergy was demonstrated between 7-hydroxytropolone and certain aminoglycosides against bacteria which were resistant to those aminoglycosides by virtue of a 2"-O-adenylyltransferase. The synthesis and characterization of some analogs of 7-hydroxytropolone is also described.
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003508:Cycloheptanes / Q000096:biosynthesis*; D004357:Drug Synergism; D005285:Fermentation; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D013302:Streptomyces / Q000378:metabolism*; D014334:Tropolone / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D003508:Cycloheptanes; C035995:7-hydroxytropolone; D014334:Tropolone; D009713:Nucleotidyltransferases; C020565:gentamicin 2''-nucleotidyltransferase