RESUMEN
Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.
Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Simulación del Acoplamiento Molecular , Compuestos Organofosforados , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Proliferación Celular/efectos de los fármacos , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/síntesis química , Relación Estructura-Actividad , Células MCF-7 , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/antagonistas & inhibidores , Femenino , Descubrimiento de Drogas , Estructura Molecular , Relación Dosis-Respuesta a Droga , FlavanonasRESUMEN
This study presents a phytochemical analysis of the leaves of Paramignya trimera, revealing the isolation of a new apotirucallane-type protolimonoid, identified as 25-O-methyl-1,2-dihydroprotoxylocarpin D (1), along with two known compounds (2 and 3). The known compounds were identified as (20S,21R,23R)-21,23-epoxy-7α,24,25-trihydroxy-21-O-methyl-3-oxoapotirucalla-14-ene (2) and 7α,24,25-trihydroxy-3-oxoapotirucalla-14-en-21,23-olide (3). The three apotirucallane-type protolimonoids (1-3) did not exhibit cytotoxicity against MCF-7 cells at a concentration of 100 µM. Interestingly, when MCF-7 cells were treated with compound 1 at various concentrations, a notable stimulatory response was observed, leading to a significant increase in cell viability, up to 127%.
