Synthesis and Biological Evaluation of Triazole-Vanillin Molecular Hybrids as Anti-Cancer Agents

Background: Triazole based drugs are widely used in cancer patients for the treatment of lifethreatening invasive fungal infections. A recent report on the usefulness of 1,2, 3- triazole scaffold for the inhibition of tyrosine kinases stimulated our curiosity to design new molecules based on this moiety. Methods: A series of new heterocyclic compounds containing 1,2,3 triazole moiety tethered to substituted vanillin or isovanillin were synthesized and analysed for their anticancer activity. The cyclopentyl/ cyclohexyl ethers derived from vanillin and isovanillin were subsequently treated with MeMgI to give the carbinols. Reaction of these carbinols with TMSN3 and ZrCl4 as Lewis acid gave the desired azides. Click chemistry on azides with diverse acetylenes furnished the triazoles. The new triazole hybribs were screened o against 60 human cancer cell lines at a 10μM dose for their potential anticancer activity. Results: The two active compounds (8a, 10a) showed strong inhibitory effect against different cell lines, with highest inhibition against breast cancer panel. To elucidate the underlying molecular mechanisms, these compounds were examined for their clonogenic potential and anchorage-independent growth of estrogen receptor positive (MCF7 and T47D) and estrogen receptor negative (MDA-MB-231 and MDAMB- 468) breast cancer cells and investigated for induction apoptotic pathways. Conclusion: The outcomes from the current study will add much to the existing knowledge of the breast cancer research. This provides a rewarding conclusion and opens the way for future researchers to design and synthesize the novel active compounds against breast cancer.