Synthesis and cytotoxic evaluation of novel dimethyl [1,1'-biphenyl]-2,2'-dicarboxylates bearing 1,3,4-thiadiazole moieties.

In search of novel anticancer agents, two series of dimethyl [1,1'-biphenyl]-2,2'-dicarboxylate derivatives, 8a-8k and 9a-9k, containing both methylenedioxy and 1,3,4-thiadiazole moieties were designed and synthesized. Cytotoxicity of these compounds was evaluated in vitro against five human tumor cell lines, i.e., HepG2, KB, A549, K562, and MCF-7. The results indicated that 8h, 8j, 8k, 9d, 9g, 9h, 9j, and 9k showed notable anticancer activities comparable to or stronger than that of 5-fluorouracil, a canonical anticancer drug. Structure-activity relationships were also discussed based on the experimental data obtained.