Efficient synthesis and evaluation of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives as antiproliferative agents
- Bioorg Med Chem Lett. 2022 Nov 1:75:128978. doi: 10.1016/j.bmcl.2022.128978.
- 1. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
- 2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: [email protected].
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 amuch broaderantitumorspectrum, and the most promising compound 8 l exerted potent andbroad-spectrum antiproliferative activity toward HeLa, HCT116, MCF-7, and A549 cell lines, with IC50 values in the micromolar range of 5.98-12.58 μM, 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 findings 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.