RESUMEN
Gramine is a natural indole alkaloid with a wide range of biological activities, but its anti-gastric cancer activity is poor. Herein, a pharmacophore fusion strategy was adopted to design and synthesize a new series of indole-azole hybrids on the structural basis of gramine. Based on our previous studies, different nitrogen-containing five-membered heterocyclic rings and terminal alkyne group were introduced into the indole-based scaffold to investigate their effect on improving the anti-gastric cancer activity of gramine derivatives. Structure-activity relationship (SAR) studies highlighted the role played by terminal alkyne in enhancing the inhibitory effect, and compound 16h displayed the best antiproliferative activity against gastric cancer MGC803 cells with IC50 value of 3.74 µM. Further investigations displayed compound 16h could induce mitochondria-mediated apoptosis, and caused cell cycle arrest at G2/M phase. Besides, compound 16h could inhibit the metastasis ability of MGC803 cells. Our studies may provide a new strategy for structural optimization of gramine to enhance anti-gastric cancer activity, and provide a potential candidate for the treatment of gastric cancer.
Asunto(s)
Antineoplásicos/química , Alcaloides Indólicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/uso terapéutico , Mitocondrias/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Relación Estructura-ActividadRESUMEN
In June and July of 2003, a field survey on the vegetation of 22 Chinese alligator habitats distributed in Nanling county, Jingxian county, Guangde county, Langxi county and Xuancheng city of Anhui province was conducted, and the plant species of the habitats were recorded and analyzed. The results showed that the vegetation of the whole habitats was secondary, and there were 294 species vascular plants, belonging to 92 families. Pteioblastus amarus shrubbery could be found in all sites, and part differences of the vegetation consisted in different habitats. The relationship between Chinese alligator and habitat vegetation was also analyzed. All of these could offer some basic botanical data for the further protection of the Chinese alligator.
