Structural, Biological, DFT, and Molecular Docking Studies of NS-Donor Schiff Base Complexes of Cu(II), Ni(II), Co(II), and Cd(II): Insights into Anticancer Potential via CDK2 Inhibition

ABSTRACT Two Schiff bases, 2-(4-nitrobenzyllidene)hydrazine-1-carbothioamide ( L1 ) and (Z)-2-((E)-3-phenylallylidene)hydrazine-1-carbothioamide ( L2 ) were synthesized in high yield via the condensation of thiosemicarbazide with 4-nitrobenzaldehyde and cinnamaldehyde. Metal complexes of Cu(II), Ni(II), Co(II), and Cd(II) were synthesized using the Schiff base ligand L1, on the other hand, Co(II) and Cd(II) complexes were synthesized using the Schiff base ligand L2. The synthesized compounds were characterized through various methods, including elemental analysis and spectroscopy, to evaluate their properties. Both the ligands and complexes were tested against gram-positive bacteria ( B. cereus and S. aureus ) and gram-negative bacteria ( E. coli and P. aeruginosa ) using a disc diffusion method. Kanamycin-30 functioned as the reference standard. L1 , C2 , C4 , L2 , C5 , and C6 , exhibited modest antibacterial activity. The complexes C4 and C6 , showed a larger zone of inhibition than the other complexes against all bacterial strains. The Schiff bases and their metal complexes were assessed for cytotoxicity against brine shrimp nauplii. The unbound ligands L1 and L2 , along with their complexes C4 , and C6 , are considered fairly strong anticancer agents compared to the standard drug vincristine sulfate. The complexes C2 and C3 demonstrated reduced activity. The ligands L1 and L2 , along with their respective complexes, were considered somewhat effective anticancer agents but showed reduced activity. The molecular docking study with the CDK2 protein shows that the metal complexes exhibited a strong interaction (more than 7.1 kcal/mol) than the free ligand (less than 6.5 kcal/mol), suggesting they could be useful as anti-cancer treatments. The energy gap between HOMO and LUMO indicated that the complexes C4 , C2 , and C3 exhibited greater biological activity compared to the others. This discovery will serve as a significant resource for the development of additional anti-cancer drugs.