RESUMEN
Cytochrome P450 (CYP) enzyme inhibitory properties of six chromenylated amide compounds (CAs) from Amyris plumieri are described. Inhibition of CYP microsomes (CYP1A1, CYP1A2, CYP1B1, CYP2D6, CYP3A4 and CYP2C19) was monitored using a fluorescent assay. Potent inhibition was found against CYP1A1 with IC(50) and K(i) for CA1 (acetamide), being the lowest at 1.547 ± 1.0 µM and 0.37 µM respectively, displaying non-competitive kinetics. The selectivity for CYP1A1 was increased in CA3 (butanamide), which also exhibited cytotoxicity against breast cancer cells, MCF7 with an IC(50) of 47.46 ± 1.62 µM. Structure-activity relationship studies provide insight at a molecular level for CAs with implications in chemoprevention and chemotherapy.
Asunto(s)
Amidas/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Fitoterapia , Extractos Vegetales/uso terapéutico , Rutaceae/química , Acetamidas/aislamiento & purificación , Acetamidas/farmacología , Acetamidas/uso terapéutico , Amidas/aislamiento & purificación , Amidas/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Benzopiranos/aislamiento & purificación , Benzopiranos/farmacología , Benzopiranos/uso terapéutico , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Relación Estructura-ActividadRESUMEN
Primary cell cultures, a continuous cell line, and a diploid cell line were grown on an artificial capillary system. The cells were subsequently infected with Venezuelan equine encephalitis virus, and viral replication was studied. Extracellular fluids harvested from this system contained high titers of virus and were relatively free of cell debris.