RESUMEN
A new ryanodine-binding inhibitor, verticilide, was isolated from the cultured broth of a fungus, Verticillium sp. FKI-1033. It is a 24-membered ring cyclic depsipeptide, its structure being elucidated as cyclo[(2R)-2-hydroxyheptanoyl-N-methyl- L-alanyl](4). Verticilide inhibited ryanodine binding to ryanodine receptors in the cockroach at an IC(50) value of 4.2 microM, whereas inhibition against mouse ryanodine receptors was weak (IC(50)=53.9 microM).
Asunto(s)
Depsipéptidos/metabolismo , Depsipéptidos/farmacología , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Rianodina/antagonistas & inhibidores , Verticillium/metabolismo , Animales , Membrana Celular/metabolismo , Cucarachas , Depsipéptidos/química , Ratones , Biología Molecular , Fibras Musculares Esqueléticas/metabolismo , Unión Proteica , Relación Estructura-ActividadRESUMEN
A phenalenone compound, atrovenetinone methyl acetal, was isolated from a culture broth of Penicillium sp. FKI-1463 as an HIV-1 integrase inhibitor, and it showed anti-HIV activity in vitro. HIV-1 integrase inhibition and anti-HIV activity of two other natural phenalenones were also studied. Among the tested compounds, funalenone inhibited HIV-1 integrase with an IC50 value of 10 microM and showed the best selectivity (anti-HIV, IC50=1.7 microM; cytotoxicity, IC50=87 microM).
