Synthesis and Evaluation of Novel Thiosemicarbazone-1, 2, 3-Triazole Hybrids as Potential Anticancer Agents

Abstract

The development of novel anticancer agents is crucial in addressing the growing challenge of cancer treatment. In this study, we report the synthesis and evaluation of novel thiosemicarbazone-1, 2, 3-triazole hybrids as potential anticancer agents. Thiosemicarbazones are well-known for their metal-chelating properties and ability to induce apoptosis in cancer cells, while 1, 2, 3-triazoles are stable pharmacophores that enhance molecular interactions with biological targets. By combining these two scaffolds, we designed hybrid molecules with the aim of improving anticancer efficacy and selectivity. The synthesis involved click chemistry to incorporate the triazole ring, followed by derivatization of the thiosemicarbazone moiety. The resulting hybrids were characterized using spectroscopic techniques such as NMR and mass spectrometry. In vitro cytotoxicity assays against various human cancer cell lines, including breast, lung, and colon cancers, demonstrated significant anticancer activity. Several compounds exhibited potent inhibition of cancer cell proliferation, with IC50 values in the low micromolar range. Mechanistic studies suggested that these hybrids induce apoptosis through the generation of reactive oxygen species (ROS) and interference with metal ion homeostasis in cancer cells. These promising findings warrant further investigation of thiosemicarbazone-1, 2, 3-triazole hybrids as potential candidates for anticancer drug development.