Biological Evaluation and Antitumor Activity of Dolutegravir Derivatives Containing a 1,2,3-Triazole Linker
摘要
1,2,3-Triazole moieties with various substituent groups were introduced into the structure of dolutegravir, yielding numerous novel derivatives. These compounds exhibited excellent inhibitory activity against a range of tumor cells, including KYSE30, KYSE140, NE3, AGS, MiaPaCa2, and SKOV3 cells. Most of the compounds exhibited potent effects on MiaPaCa2 cells. Specifically, compounds 4b, 4e, 4f, and 4h demonstrated promising inhibitory activities against MiaPaCa2 cells, with IC50 values of 0.86±0.35, 1.01±0.27, 1.69±0.53, and 1.17±0.37 μM, respectively. Additionally, compounds 4b, 4e, 4f, and 4h induced apoptosis in MiaPaCa2 cells, and compounds 4e, 4f, and 4h induced cell cycle arrest in the G2/M phase. These findings suggest that dolutegravir derivatives are promising candidates for treating MiaPaCa2 tumors.