Synthesis of Zinc-Based Complexes and Their Potential Anticancer Activity Against Human Cell Lines

Background: Zinc-based coordination complexes have been envisaged as an attractive alternative to the platinum-based chemo-therapeutics, which have the potential to not only be more selective but have fewer systemic side effects. This research meets the necessity of new cancer-fighting drugs that are not only more effective but also have higher medication and treatment candidates by rationally designing zinc-based metallodrugs. Objective: To synthesize and comprehensively discuss zinc (II) complex with various ligand systems on their anti-cancerous effect on human cancer cell lines, explore structural activity relationship and mechanism of action. Methodology: Eight zinc (II) compounds (zinc-L1 to Zn-L8) were prepared by means of Schiff bases, phenanthroline derivatives and thiosemicarbazone ligands. Solid characterization was done using FT-IR, NMR, UV-Vis spectroscopy and X-ray crystallography. The evaluation of anticancer activity by using MTT assays against HeLa, MCF-7, A549 and HepG2 cell lines, and L929 fibroblast cultures was used as a normal control. Mechanistic studies had: flow cytometry to examine apoptosis, cell cycle control, oxidative damage and DNA fragmentation. Results: All complexes were found to have high cytotoxic effects and their IC50 values were between 5.2 45.8 μM. Complex Zn-L3 showed an outstanding activity in terms of killing MCF-7cells (IC 50 = 5.2muM) and excellent selectivity index values (2.9-8.9), which were better than those of cisplatin (2.1). Mechanistic study showed the multitarget effects of boosted ROS formation (285% control), G2/M phase cell cycle block (45. 8%), and strong induction of apoptosis (68. 4%). The structure activity relationships established that heterocyclic ligands high in nitrogen that bind as tetrahedra were the most desirable molecules with anticancer activity. Conclusion: The synthesized zinc complexes exhibit outstanding anticancer features with multi-target effect surpassing standard platinum anticancer compounds. The results make zinc metallodrugs possible candidates to propose as a new generation of metal-based chemotherapeutics that will be first to target and more likely to be less toxic than existing metal-based chemotherapeutics.