Design, synthesis, and biological evaluation of novel alkylsulfanyl-1,2,4-triazoles as cis-restricted combretastatin A-4 analogues

Abstract Thirty-two novel 3-alkylsulfanyl-1,2,4-triazole derivatives, designed as cis -restricted combretastatin A-4 analogues, were synthesized and evaluated for their antiproliferative activities. The results indicated that analogue 20 showed more potent antiproliferative activities against PC-3 cell lines than positive control CA-4. Particularly, the most promising compound 25 displayed 5-fold improvement compared to CA-4 in inhibiting HCT116 cell proliferation with IC 50 values of 1.15 μM. Further flow-activated cell sorting analysis revealed that compound 20 displayed a significant effect on G 2 /M cell-cycle arrest in a dose-dependent manner in PC-3 cells. From this study, analogues 20 and 25 were the most potent anti-cancer agents in this structural class, and were considered lead compounds for further development as anti-cancer drugs.