RESUMEN
In the current study, new benzimidazole-based 1,3,4-oxadiazole derivatives have been synthesized and characterized by NMR, IR, MS, and elemental analysis. The final compounds were screened for cytotoxicity against MDA-MB-231, SKOV3, and A549 cell lines and EGFR for inhibitory activities. Compounds 10 and 13 were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC50 0.33 and 0.38 µM, respectively, comparable to erlotinib (IC50 0.39 µM). Furthermore, these two compounds effectively suppressed cell cycle progression and induced cell apoptosis in MDA-MB-231, SKOV3, and A549 cell lines. The docking studies revealed that these compounds showed interactions similar to erlotinib at the EGFR site. It can be concluded that the synthesized molecules effectively inhibit EGFR, can arrest the cell cycle, and may trigger apoptosis and therefore, could be used as lead molecules in the development of new anticancer agents targeting EGFR kinase.
Asunto(s)
Antineoplásicos , Inhibidores de Proteínas Quinasas , Ensayos de Selección de Medicamentos Antitumorales , Clorhidrato de Erlotinib/farmacología , Inhibidores de Proteínas Quinasas/química , Receptores ErbB/metabolismo , Antineoplásicos/química , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Proliferación Celular , Apoptosis , Puntos de Control del Ciclo Celular , Bencimidazoles/farmacología , Doxorrubicina/farmacología , Relación Estructura-ActividadRESUMEN
An environmentally friendly non-thermal DC plasma reduction route was adopted to reduce Ag+ ions at the plasma−liquid interface into silver nanoparticles (AgNPs) under statistically optimized conditions for biological and photocatalytic applications. The efficiency and reactivity of AgNPs were improved by statistically optimizing the reaction parameters with a Box−Behnken Design (BBD). The size of the AgNPs was chosen as a statistical response parameter, while the concentration of the stabilizer, the concentration of the silver salt, and the plasma reaction time were chosen as independent factors. The optimized parameters for the plasma production of AgNPs were estimated using a response surface methodology and a significant model p < 0.05. The AgNPs, prepared under optimized conditions, were characterized and then tested for their antibacterial, antioxidant, and photocatalytic potentials. The optimal conditions for these three activities were 3 mM of stabilizing agent, 5 mM of AgNO3, and 30 min of reaction time. Having particles size of 19 to 37 nm under optimized conditions, the AgNPs revealed a 82.3% degradation of methyl orange dye under UV light irradiation. The antibacterial response of the optimized AgNPs against S. aureus and E. coli strains revealed inhabitation zones of 15 mm and 12 mm, respectively, which demonstrate an antioxidant activity of 81.2%.