Synthesis, antiproliferative evaluation, and structure-activity relationships of novel triazole-isoindoline hybrids bearing 3,4,5-trimethoxyphenyl moiety

As an aspect of our ongoing research on developing novel antiproliferative agents, 31 new triazole-isoindoline hybrids bearing 3,4,5-trimethoxyphenyl moiety were synthesized and evaluated for their antiproliferative activity against four cancer cell lines (HepG2, HeLa, PC-3, and HCT116). Some compounds showed excellent potency, and compared to fluorouracil, the most promising compound 6s exhibited 5.8-, 4.3-, and 1.3- fold increase in activities against HeLa, HepG2, and PC-3 cell lines with IC50 values of 9.7, 10.7, and 16.8 mu M, respectively. Moreover, structure-activity relationship studies indicated that a much shorter amide linkage and electron-withdrawing groups at phenyl ring of the acetamide fragment contribute to the antitumour activity.