RESUMEN
Cytisine-pterocarpan-derived compounds were biomimetically synthesized with (-)-cytisine and (-)-maackiain via a N,N-4-dimethyl-4-aminopyridine (DMAP)-mediated synthetic strategy in a mild manner. In the present study, tonkinensine B (4) was elaborated in good and high yields with the optimized reaction conditions. The in vitro cytotoxicity of compound 4 was evaluated against breast cancer cell lines and showed that 4 had a better cytotoxicity against MDA-MB-231 cells (IC50 = 19.2 µM). Depending on the research on cytotoxicities of 4 against RAW 264.7 and BV2 cells, it was suggested that 4 produced low cytotoxic effects on the central nervous system. Further study indicated that 4 demonstrated cytotoxic activity against MDA-MB-231 cells and the cytotoxic activity was induced by apoptosis. The results implied that the apoptosis might be induced by mitochondrion-mediated apoptosis via regulating the ratio of Bax/Bcl-2 and promoting the release of cytochrome c from the mitochondrion to the cytoplasm in MDA-MB-231 cells.
Asunto(s)
Neoplasias de la Mama/metabolismo , Citocromos c/metabolismo , Compuestos Heterocíclicos con 2 Anillos/síntesis química , Compuestos Heterocíclicos con 2 Anillos/farmacología , Mitocondrias/metabolismo , Alcaloides/química , Animales , Azocinas/química , Mimetismo Biológico , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Compuestos Heterocíclicos con 2 Anillos/química , Humanos , Células MCF-7 , Ratones , Estructura Molecular , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Pterocarpanos/química , Quinolizinas/química , Células RAW 264.7 , Proteína X Asociada a bcl-2/metabolismoRESUMEN
In vitro interaction of fluconazole and baicalein (BE) was investigated against 30 fluconazole-resistant clinical isolates of Candida albicans. Synergistic activities were determined using the checkerboard microdilution assay based on the fractional inhibitory concentration indices. Organisms were also tested against the 2 drugs singly and in combination using time-kill methods. Both fluconazole and BE showed weak antifungal activity when tested alone. However, the combination of fluconazole and BE showed strong antifungal activity against most of the fluconazole-resistant isolates tested. The findings of time-kill curves confirmed the interaction. Yeast cells grown in the presence of BE exhibited a reduced extrusion of Rhodamine 6G, which indicates the inhibition of efflux pumps by BE. This novel synergism of fluconazole and BE that can overcome drug-resistance in yeast may prove useful in combined treatment of fungal infections.