Efficient synthesis and evaluation of novel 6-arylamino-[1,2,4]triazolo [4,3-a]pyridine derivatives as antiproliferative agents

Based on our previous work, a series of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives were synthesized, and evaluated for antiproliferative activities. SAR studies revealed that inserting an amino linkage between 6-aryl group and [1,2,4]triazolo[4,3-a]pyridine core led to a much broader antitumor spectrum, and the most promising compound 8 l exerted potent and broad-spectrum antiproliferative activity toward HeLa, HCT116, MCF-7, and A549 cell lines, with IC50 values in the micromolar range of 5.98-12.58 mu M, which were more active than the positive control 5-FU. The mechanism investigation illustrated that 8 l dose-dependently caused cell cycle arrest at the G2/M phase, and induced cell apoptosis in HeLa cells. Consequently, these find-ings suggest the 6-arylamino-[1,2,4]triazolo[4,3-a]pyridines afford significant potential for the discovery of a new highly efficient anticancer agents.

Automated summary

A novel series of 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives were synthesized and evaluated for their antiproliferative activities. Inserting an amino linkage between the 6-aryl group and [1,2,4]triazolo[4,3-a]pyridine core resulted in a broader antitumor spectrum. Compound 8l exhibited potent and broad-spectrum antiproliferative activity, inducing cell cycle arrest and apoptosis. These findings suggest significant potential for the discovery of new highly efficient anticancer agents.