RESUMEN
Phytoestrogens, including miroestrol and deoxymiroestrol, have the ability to act through competition with estrogen for binding to the estrogen receptor (ER). Here, we utilize manual ligand docking followed by molecular dynamics simulations and binding free energy calculations with the linear interaction energy method to predict the binding modes and the binding affinities of phytoestrogens on the ligand binding domain of ER (ERalpha-LBD). The calculations brought about the good correlation between the calculated binding free energy and the bioassays. Furthermore, consideration of Lennard-Jones and Coulomb interaction energies of miroestrol and deoxymiroestrol on ERalpha-LBD provided the information to develop the phytoestrogen derivatives as the preferred drug for ER positive breast cancer treatment.
Asunto(s)
Antineoplásicos Fitogénicos/química , Descubrimiento de Drogas/métodos , Receptor alfa de Estrógeno/agonistas , Receptor alfa de Estrógeno/química , Fitoestrógenos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Simulación por Computador , Cumarinas/química , Cumarinas/farmacología , Cumarinas/uso terapéutico , Entropía , Humanos , Modelos Químicos , Estructura Molecular , Fitoestrógenos/farmacología , Fitoestrógenos/uso terapéutico , Electricidad Estática , Esteroides/química , Esteroides/farmacología , Esteroides/uso terapéutico , TermodinámicaRESUMEN
Twenty constituents were isolated from the n-hexane and chloroform extracts of Aristolochia constricta, a plant whose aerial parts have been used empirically in folk medicine for various purposes. The inhibitory effects of these constituents on smooth muscle contraction in isolated guinea-pig ileum were studied in order to observe their antispasmodic effects. 3,4-Dibenzyldihydrofuran-type lignans [(-)-cubebin, (-)-hinokinin, and (-)-pluviatolide] and a kaurene-type diterpene [(-)-kaur-16-en-19-oic acid] were isolated as active principals. They inhibited electrically induced and acetylcholine-induced contraction in the isolated guinea-pig ileum. In addition, 9- O-[(-)-kaur-15-en-17-oxyl]cubebin was isolated as a new diterpeno-lignan hybrid, although this constituent did not exhibit antispasmodic activity.