Synthesis, in vitro and in vivo anticancer activities of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine-3,5-dione derivatives

Abstract

To develop potent and selective anticancer agents, a series of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine-3,5-dione derivatives were designed and synthesized. All the compounds were evaluated for their antiproliferative activities against a panel of four human cancer cell lines. Among them, compound 4u is the most potent, exhibiting IC₅₀ values ranging from 5.1 to 10.1 μM. Flow cytometry and western blot analyses revealed that treatment of MGC-803 cells with compound 4u induces early cellular apoptosis via activation of caspases-9/3. Furthermore, compound 4u effectively reduced the tumor growth exhibited by human gastric cancer cells in vivo without obvious adverse side effects. Our findings indicate that compound 4u may serve as a lead compound to target solid tumors.