title: Critical role of a methyl group on the γ-lactone ring of annonaceous acetogenins in the potent inhibition of mitochondrial complex I.
abstract: C34-epi and C34-epi-C35-trifluoro analogues of solamin, a mono-THF annonaceous acetogenin, were synthesized. Their inhibitory activity, along with previously synthesized analogues (C35-fluoro, C35-difluoro, and C35-trifluorosolamins), against bovine mitochondrial NADH-ubiquinone oxidoreductase (complex I) was determined. The present study revealed that the methyl group on the γ-lactone moiety is critical to the potent inhibition of complex I by natural acetogenins.
authors: Kyoto Pharmaceutical University, 1 Shichono-cho, Yamashina-ku, Kyoto 607-8412, Japan. kojima@mb.kyoto-phu.ac.jp
authors: Naoto
authors: N
authors: Kojima
authors: Masato
authors: M
authors: Abe
authors: Yuki
authors: Y
authors: Suga
authors: Kazufumi
authors: K
authors: Ohtsuki
authors: Tetsuaki
authors: T
authors: Tanaka
authors: Hiroki
authors: H
authors: Iwasaki
authors: Masayuki
authors: M
authors: Yamashita
authors: Hideto
authors: H
authors: Miyoshi
mesh_terms: D054378:Acetogenins / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D054378:Acetogenins; D007783:Lactones; D042967:Electron Transport Complex I