Elucidating the Therapeutic Mechanisms of Nickel(II)– Hydroazinecarbothioamide Complexes Across Cancer, Microbial, and Oxidative Stress Models

Abstract

Isatin‐based ligands have been recognized for their remarkable pharmacological potential and this study reports the synthesis, characterization, and biological evaluation of three novel nickel(II)‐isatin hydrazone complexes ( C1–C3 ). The complexes were characterized by FT‐IR, UV–vis, mass spectroscopy, DFT, magnetic, conductivity and thermal analyses indicating octahedral geometry and appreciable heat stability. Molecular electrostatic potential mapping gave information on their electronic properties. DFT calculations indicated decreased HOMO–LUMO gaps indicating increased reactivity. Biological screening showed remarkable anticancer activity against HCT‐116, A549, MCF‐7, and HepG‐2 cell lines (IC 50 = 7.22–17.33 µM), potent antibacterial and antifungal activities comparable to ciprofloxacin and clotrimazole against Staphylococcus aureus and Candida albicans , and significant antioxidant activity with 59%–69% of the radical scavenging. Molecular docking and dynamics studies showed the stable binding interactions with the target enzyme FabH especially for complex C3 . These results collectively highlight C1‐C3 as multifunctional therapeutic candidates with stability and reactivity properties, making them attractive scaffolds for pharmacological development.