Exploring the Anticancer and Antimicrobial Activities of Transition Metal Chelates Derived From Hydrazones: Synthesis, Spectral Investigation, Molecular Docking, and ADMET Profiling

In this study, hydrazine ligands were synthesized from thiophene-2-carboxylic acid/benzo[b]thiophene-2-carboxylic acid hydrazides and 1,3-diphenyl-1H-pyrazole-4-carbaldehyde, along with their Co(II), Ni(II), Cu(II), and Zn(II) complexes. The synthesized compounds were thoroughly characterized and originally evaluated for their anticancer and antimicrobial potentials. Building on these findings, the compounds were evaluated against A549 and DU145 cancer cells, the IMR-90 cell line, and clinically relevant microbial strains. Among them, the Cu(II) and Zn(II) complexes (9, 10) emerged as most active, with the Cu(II) complex (9) showing pronounced anticancer efficacy against both cancer cell lines while maintaining lower sensitivity toward IMR-90 cells. Remarkably, the Cu(II) (9) and Zn(II) (6, 10) complexes exhibited outstanding antimicrobial activity, with MIC values (0.0052-0.0104 µmol/mL) comparable to those of established reference drugs, underscoring their strong therapeutic potential. Molecular docking supported the observed bioactivities, with compound (9) showing strong binding to the 4ZXT protein (-9.98 kcal/mol). Similarly, compound (10) revealed favorable binding with target protein, yielding docking scores of -9.43 kcal/mol. These interactions confirm the compounds' strong biological affinity and therapeutic potential. ADMET results indicate favorable pharmacokinetics, supporting their drug-likeness. Their broad bioactivity provides a solid basis for future clinical studies and novel drug development.