title: Design, synthesis, and antifungal activity of inhibitors of brassilexin detoxification in the plant pathogenic fungus Leptosphaeria maculans.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
authors.forename: M Soledade C
authors.initials: MS
authors.lastname: Pedras
authors.forename: Mojmir
authors.initials: M
authors.lastname: Suchy
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D007211:Indoles; D010936:Plant Extracts; D012717:Sesquiterpenes; D013729:Terpenes; D013844:Thiazoles; C430121:brassilexin; D000094162:Phytoalexins