Synthesis of new Cu (II) and Zn (II) complexes derived from isatin-3-thiosemicarbazone: X-ray, anticancer activity, molecular docking, ADMET study, and quantum chemical calculations

The current work aimed to synthesize new mononuclear Cu (II) and Zn (II) complexes derived from isatin-based thiosemicarbazide, (Z)-N-methyl-2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamide ligand (L1) using the reflux conventional method. Structural characterization for the synthesized compounds was achieved via elemental analyses, spectroscopic analysis, magnetic susceptibility, molar conductivity, and thermal analysis. The compounds were further explored for their prospective anticancer properties with the aid of in silico methodology. Complexation of metal centers with L1 was observed using the shifting of the v(C=N) peak to lower frequencies and the emergence of new peaks in the range of 454–512 cm⁻¹ assigned to v(M-N) and v(M-O). The non-electrolytic character of Cu²⁺ and Zn²⁺ compounds was displayed by their low molar conductivities. Quantum chemical calculations were employed to investigate the electronic and molecular properties of the complexes. The frontier molecular orbitals were performed by density functional theory (DFT) calculations to provide valuable information regarding their molecular orbitals, reactivity indices, and electronic structures, assisting in understanding their structure–activity relationships and potential mechanisms of action. Additionally, molecular docking was carried out to comprehend the interaction of the compounds with the selected enzyme and determine their potential binding mode and energy. Meanwhile, the ADMET study exhibited that all of the compounds possess good oral bioavailability suggesting potent and suitable anticancer drug candidates. All the compounds were tested against human leukemia K562 cancer cell line and human fibroblasts Hs27 cell line. Overall, this comprehensive study highlights the synthesis, characterization, anticancer activity, molecular docking, ADMET evaluation, and quantum chemical calculations of new Cu (II) and Zn (II) complexes derived from isatin-3-thiosemicarbazone.