RESUMEN
Minnamide A is a lipopeptide with a unique repeating structure consisting of hydroxy and proposed ß-branched methyl groups. The absolute configuration of minnamide A was determined by a combination of chemical degradation, chiral HPLC analyses, and synthetic methods. Minnamide A showed growth-inhibitory activity toward HeLa cells with an IC50 value of 0.17 µM and rapidly induced cell death at a concentration of 2 µM. Minnamide A induced the copper-mediated accumulation of reactive oxygen species.
Asunto(s)
Cianobacterias/química , Lipopéptidos/farmacología , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Lipopéptidos/química , Lipopéptidos/aislamiento & purificación , Conformación Molecular , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-ActividadRESUMEN
In 2014, the γ-pyrone-containing polyketide, yoshinone A, was isolated from the marine cyanobacterium Leptolyngbya sp. and its structure was determined. Yoshinone A inhibited differentiation of 3T3-L1 cells into adipocytes, with an EC50 value of 420 nM without any cytotoxicity, and therefore is expected to be a lead compound for obesity drugs. To establish its absolute configuration, and to provide sufficient amounts for further research, the total synthesis of yoshinone A was achieved through synthesis of its two possible diastereomers.