Evidence of steric factors in the fungitoxic mechanisms of 8-quinolinol and its 5- and 7-halogenated analogues.
Antifungal studies were made of mixtures of minimal inhibitory concentrations (MICs) of 8-quinolinol and its 5- and 7-halo analogues against six fungi: Aspergillus niger, A. oryzae, Trichoderma viride, Myrothecium verrucaria, Mucor cirinelloides, and Trichophyton mentagrophytes. Mixtures of 8-quinolinol with 5- or 7-fluoro-8-quinolinol and of 5- and 7-fluoro-8-quinolinol showed additive activity, and their respective toxicities were reversed by L-cysteine. These results suggested a common mechanism of activity for the three toxicants. Potentiation of the fungitoxicity of mixtures of 8-quinolinol and its 5- and 7-chloro, bromo, and iodo analogues, as well as mixtures of 5- and 7-chloro, 5- and 7-bromo, and 5- and 7-iodo-8-quinolinols, along with the absence of protection of the fungi by L-cysteine from the toxicities of these compounds was observed. This suggested that the modes of action of these compounds were different from each other and from 8-quinolinol and the 5- and 7-fluoro analogues. The geometry of 8-quinolinol as influenced by substituents in the 5- and 7- positions of the molecule determines its site(s) of fungitoxicity.
Gershon
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Fordham University, Department of Chemistry, Bronx, NY 10458.
Clarke
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Gershon
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D000935:Antifungal Agents / Q000494:pharmacology*; D001234:Aspergillus niger / Q000187:drug effects; D001236:Aspergillus oryzae / Q000187:drug effects; D003545:Cysteine / Q000494:pharmacology; D004347:Drug Interactions; D006219:Halogens / Q000494:pharmacology; D006912:Hydroxyquinolines / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009089:Mucor / Q000187:drug effects; D015125:Oxyquinoline / Q000031:analogs & derivatives / Q000494:pharmacology; D014242:Trichoderma / Q000187:drug effects; D014249:Trichophyton / Q000187:drug effects
D000935:Antifungal Agents; D006219:Halogens; D006912:Hydroxyquinolines; D015125:Oxyquinoline; D003545:Cysteine