Multi-target bioactive M(II) pyridine-diamine complexes: synthesis, characterization, in vitro and in silico evaluation

In this study, we synthesized Co(II), Zn(II), and Cd(II) complexes based on a pyridine-derived ligand ( N 1 , N 1 -diethyl -N 2 -(pyridin-2-ylmethyl)ethane-1,2-diamine, DEP-R ). Single-crystal X-ray diffraction analysis confirmed that all complexes possessed distorted trigonal bipyramidal geometries. The complexes exhibited significant potential against both Jack bean (JB) and Bacillus pasteurii (BP) ureases. Notably, the Cd(DEP-R)Br 2 complex exhibited considerable inhibitory potency against urease (IC 50 = 4.51 ± 0.13 and 5.71 ± 0.14 μM for JB and BP, respectively), outperforming the standard inhibitor Thiourea (IC 50 = 11.0 ± 0.62 and 9.10 ± 0.73 μM, respectively). In antioxidant assays, Co(DEP-R)Cl 2 displayed the highest DPPH radical scavenging activity. Additionally, all metal complexes showed a superior in vitro anti-diabetic activity compared to both the standard drug and the uncomplexed DEP-R ligand. Molecular docking results showed that Cd(DEP-R)Br 2 and Co(DEP-R)Cl 2 formed multiple favorable interactions (hydrogen bonding, ionic, and π interactions) with the active sites of urease, Leishmania major oxidoreductase, and human pancreatic α-amylase, supporting their promising in vitro activity. ADMET analysis predicted high GI absorption, Lipinski compliance, moderate solubility, good bioavailability, and low cardiotoxicity, with some neurological and respiratory toxicity risks. DFT-based HOMO–LUMO analysis confirmed the stability and reactivity of the complexes. Overall, the present compounds are promising multi-target metallodrug scaffolds. • Co(II), Zn(II), and Cd(II) pyridine–diamine complexes were synthesized and structurally characterized. • Single-crystal X-ray analysis confirmed distorted trigonal bipyramidal geometries. • The Cd(II) complex showed superior urease inhibition, surpassing thiourea. • Metal complexation markedly enhanced anti-leishmanial, antioxidant, and α-amylase activities. • Docking, ADMET, and DFT studies supported strong multi-target binding and drug-likeness.