Tranilast-tyrosine hybrid molecule exhibits dual activity: suppression of epithelial-mesenchymal transition and induction of cytotoxicity in cancer cells

The anti-allergic drug tranilast (TNL) reportedly exhibits inhibitory activity against epithelial-mesenchymal transition (EMT) at high concentrations. Herein, we synthesized a new hybrid molecule, tyrosine-conjugated TNL having a propyl linker (TNL-T), which is expected to increase anti-EMT activity by enhancing intracellular delivery through an amino acid transporter expressed in cancer cells. The anti-EMT activity of TNL-T was similar to that of TNL in the lung carcinoma cell line A549. Unlike TNL, TNL-T could induce dose-dependent cytotoxicity in A549 cells; this cytotoxicity was also observed in the glioblastoma cell lines U251 and U87. However, neither tyrosine nor TNL exhibited such cytotoxicity, demonstrating the importance of the TNL-T structure. The derivatization study showed that a derivative with an ethyl linker has the similar functions, and that of a pentyl linker was inactive. TNL-T, which exhibited dual activity by suppressing EMT and cancer cell proliferation, could aid in the development of new anticancer drugs.