Design, Synthesis and Biological Evaluation of [1,2,4]Triazolo[1,5-]pyrimidine Indole Derivatives against Gastric Cancer Cells MGC-803 via the Suppression of ERK Signaling Pathway.

[1,2,4]Triazolo[1,5-]pyrimidine and indole skeletons are widely used to design anticancer agents. Therefore, in this work, a series of [1,2,4]triazolo[1,5-]pyrimidine indole derivatives were designed and synthesized by the molecular hybridization strategy. The antiproliferative activities of the target compounds - against three human cancer cell lines, MGC-803, HCT-116 and MCF-7, were tested. Among them, compound exhibited the most active antiproliferative activities against MGC-803, HCT-116 and MCF-7 cells, with IC values of 9.47, 9.58 and 13.1 μM, respectively, which were more potent than that of the positive drug . In addition, compound could dose-dependently inhibit the growth and colony formation of MGC-803 cells. Compound exhibited significant inhibitory effects on the ERK signaling pathway, resulting in the decreased phosphorylation levels of ERK1/2, c-Raf, MEK1/2 and AKT. Furthermore, compound induced cell apoptosis and G2/M phase arrest, and regulated cell cycle-related and apoptosis-related proteins in MGC-803 cells. Taken together, we report here that [1,2,4]triazolo[1,5-]pyrimidine indole derivatives, used as anticancer agents via the suppression of ERK signaling pathway and the most active compound, , might be a valuable hit compound for the development of anticancer agents.