title: Cubebin and derivatives as inhibitors of mitochondrial complex I. Proposed interaction with subunit B8.
abstract: The effects on mitochondrial respiration and complex I NADH oxidase activity of cubebin and derivatives were evaluated. The compounds inhibited the state 3 glutamate/malate-supported respiration of hamster liver mitochondria with IC(50) values ranging from 12.16 to 83.96 microM. NADH oxidase reaction was evaluated in submitochondrial particles. The compounds also inhibited this activity, showing the same order of potency observed for effects on state 3 respiration, as well as a tendency towards a non-competitive type of inhibition (K(I) values ranging from 0.62 to 16.1 microM). A potential binding mode of these compounds with complex I subunit B8, assessed by docking calculations, is proposed.
authors.affiliation: Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Saraiva
authors.forename: Claudia Meirelles
authors.initials: CM
authors.lastname: Siqueira
authors.forename: Carlos Henrique Tomich
authors.initials: CH
authors.lastname: de Paula da Silva
authors.forename: Vinicius
authors.initials: V
authors.lastname: Barreto da Silva
authors.forename: Valeria Gomes
authors.initials: VG
authors.lastname: Tudella
authors.forename: Rosangela
authors.initials: R
authors.lastname: Silva
authors.forename: Marcio Luis
authors.initials: ML
authors.lastname: Andrade E Silva
authors.forename: Daniel Junqueira
authors.initials: DJ
authors.lastname: Dorta
authors.forename: Jairo Kenupp
authors.initials: JK
authors.lastname: Bastos
authors.forename: Sergio Akira
authors.initials: SA
authors.lastname: Uyemura
authors.forename: Sergio
authors.initials: S
authors.lastname: de Albuquerque
authors.forename: Carlos
authors.initials: C
authors.lastname: Curti
mesh_terms: D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007700:Kinetics; D017705:Lignans / Q000737:chemistry* / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
chemical_list: D017705:Lignans; D009097:Multienzyme Complexes; D021122:Protein Subunits; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; C433065:cubebin