title: Design, syntheses, and kinetic evaluation of 3-(phenylamino)oxazolidine-2,4-diones as potent cytochrome bc₁ complex inhibitors.
abstract: The cytochrome bc₁ complex (EC 1.10.2.2, bc₁) is one of the most promising targets for new drugs and agricultural fungicides. Among the existing bc₁ complex inhibitors specifically binding to the Q(o) site, oxazolidinedione derivatives have attracted great attention. With the aim to understand the substituent effects of oxazolidinedione derivatives on the inhibition activity against the bc₁ complex, a series of new oxazolidinedione derivatives were designed, synthesized, and biologically evaluated. The further inhibitory kinetics studies against porcine succinate-cytochrome c reductase (SCR) revealed that the representative compound 8d and famoxadone are both non-competitive inhibitors with respect to the substrate cytochrome c, but competitive inhibitors with respect to substrate decylubiquinol (DBH₂). In addition, compound 8d and famoxadone showed, respectively, 35-fold and 15-fold greater inhibitory activity against the porcine SCR than the porcine bc₁ complex, indicating that these two inhibitors not only inhibited the activity of the bc₁ complex, but possibly affect the interaction between the complex II and the bc₁ complex. To our knowledge, this is the first report that famoxadone and its analogs have effects on the interaction between the complex II and the bc₁ complex.
authors: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors: Fu
authors: F
authors: Wang
authors: Hui
authors: H
authors: Li
authors: Le
authors: L
authors: Wang
authors: Wen-Chao
authors: WC
authors: Yang
authors: Jia-Wei
authors: JW
authors: Wu
authors: Guang-Fu
authors: GF
authors: Yang
mesh_terms: D000818:Animals; D015195:Drug Design; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010080:Oxazoles / Q000737:chemistry* / Q000494:pharmacology*; D013384:Succinate Cytochrome c Oxidoreductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D010080:Oxazoles; C064210:oxazolidine; D013384:Succinate Cytochrome c Oxidoreductase; D014450:Electron Transport Complex III