Synthesis of Zinc-Based Complexes and Their Potential Anticancer Activity Against Human Cell Lines
Department of Chemistry, College of Education for Pure sciences, University of Kirkuk, Kirkuk, Iraq.
Open Access Research Journal of Chemistry and Pharmacy, 2025, 07(01), 005–020
Article DOI: 10.53022/oarjcp.2025.7.1.0015
Publication history:
Received on 27 July 2025; revised on 06 September 2025; accepted on 08 September 2025
Abstract:
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.
Keywords:
Zinc Complexes; Anticancer Activity; Cytotoxicity; Apoptosis; Metallodrugs
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