Synthesis and biological evaluation of novel farnesylthiosalicylic acid derivatives for cancer treatment.

Novel farnesylthiosalicylic acid (FTS) derivatives were synthesized by coupling with different substituted diamines. Their in vitro growth inhibitory activities against seven human cancer cell lines were evaluated. The results revealed that the synthetic farnesylthiosalicylamides displayed significant antitumor activities compared to the positive control FTS. Especially, compound 8f exhibited the strongest antitumor activities with IC50 values of 6.20-7.83 µM, which were one- to threefold less than those of sorafenib and six- to tenfold less than that of FTS against each cell line in vitro. Furthermore, 8f could inhibit the Ras-related signaling pathway and induce SMMC-7721 cell apoptosis superior to FTS in a dose-dependent manner. These data indicate that 8f may hold greater promise as therapeutic agent for the intervention of human cancers.