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Cubebin and derivatives as inhibitors of mitochondrial complex I. Proposed interaction with subunit B8 |
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| Authors: | Juliana Saraiva Claudia Meirelles Siqueira Carlos Henrique Tomich de Paula da Silva Vinicius Barreto da Silva Valeria Gomes Tudella Rosângela Silva |
| Affiliation: | 1. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeir?o Preto, Universidade de S?o Paulo, Avenida do Café, s/n, CEP 14040-903 Ribeir?o Preto, SP, Brazil;2. Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeir?o Preto, Universidade de S?o Paulo, Avenida do Café, s/n, CEP 14040-903, Ribeir?o Preto, SP, Brazil;3. Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeir?o Preto, Universidade de S?o Paulo, Avenida do Café, s/nCEP 14040-903, Ribeir?o Preto, SP, Brazil;4. Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, CEP 14404-600 Franca, SP, Brazil |
| 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 IC50 values ranging from 12.16 to 83.96 μM. 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 (KI values ranging from 0.62 to 16.1 μM). A potential binding mode of these compounds with complex I subunit B8, assessed by docking calculations, is proposed. |
| Keywords: | Cubebin mitochondria mitochondrial complex I CI-B8 NADH oxidase inhibition |