Design, synthesis, and antifungal activity of inhibitors of brassilexin detoxification in the plant pathogenic fungus Leptosphaeria maculans.
Potential inhibitors of Leptosphaeria maculans mediated detoxification of the phytoalexin brassilexin were designed and synthesized based on the planar heteroaromatic structure of isothiazolo[5,4-b]indole. Screening of these compounds for inhibition of brassilexin detoxification in cultures of L. maculans indicated that 4-(2-chlorophenyl)isothiazole had the largest effect on the rate of brassilexin detoxification. However, the most antifungal compound among the potential inhibitors, isothiazolo[5,4-b]quinoline, did not appear to affect the metabolism of brassilexin noticeably, suggesting that growth inhibition is not sufficient to slow down the rate of brassilexin detoxification. Furthermore, it was determined that 4-arylisothiazoles as well as isothiazolo[5,4-b]thianaphthene displayed antifungal activity against L. maculans.
Pedras
M Soledade C
MS
Department of Chemistry, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
Suchy
Mojmir
M
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001203:Ascomycota / Q000187:drug effects* / Q000378:metabolism* / Q000472:pathogenicity; D001681:Biological Assay; D001711:Biotransformation / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D007211:Indoles / Q000378:metabolism*; D007700:Kinetics; D015394:Molecular Structure; D010936:Plant Extracts / Q000378:metabolism; D010944:Plants / Q000378:metabolism / Q000382:microbiology*; D012717:Sesquiterpenes; D013729:Terpenes; D013844:Thiazoles / Q000378:metabolism*; D000094162:Phytoalexins
D000935:Antifungal Agents; D007211:Indoles; D010936:Plant Extracts; D012717:Sesquiterpenes; D013729:Terpenes; D013844:Thiazoles; C430121:brassilexin; D000094162:Phytoalexins