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

In this study, we synthesized Co(II), Zn(II), and Cd(II) complexes based on a pyridine-derived ligand (N¹,N¹-diethyl-N²-(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)Br₂] complex exhibited considerable inhibitory potency against urease (IC₅₀ = 4.51 ± 0.13and 5.71 ± 0.14μM for JB and BP, respectively), outperforming the standard inhibitor Thiourea (IC₅₀ = 11.0 ± 0.62 and 9.10 ± 0.73μM, respectively). In antioxidant assays, [Co(DEP-R)Cl₂] 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)Br₂] and [Co(DEP-R)Cl₂] 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.