Some Co(II)-Schiff base complexes as promising anticancer agents: A DFT and molecular docking study

Abstract

Non-covalent interactions have long been an emerging area of research in anticancer drug-DNA binding investigations since in vivo biomolecules are the primary target sites for all types of drug molecules. This study delves into the interaction of five promising Co(II)-Schiff base complexes (M₁-M₅) with DNA nucleobases, employing a multi-pronged approach to unveil their anticancer activity and interaction mechanisms. Density functional theory (DFT) provided a deep dive into the complexes' electronic structures, shedding light on how they interact with DNA nucleobases, their stability within these interactions, and the overall geometry involved. Further insights were gleaned from analysing frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), and non-covalent interactions (NCI) to investigate other important aspects of Co(II)-Schiff base complexes with the receptor AT/GC base pairs. Moreover, molecular docking simulations predicted the preferred binding sites and orientations of these complexes with B-DNA dodecamer, offering a realistic picture of their interactions with DNA in a larger context. Further, we also carried out Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies to analyse the pharmacokinetic and physicochemical properties of the Co(II)-Schiff base complexes. DFT study suggest that the Complex M₁ exhibits a strong affinity for both AT and GC base pairs, as indicated by its high negative interaction energy values of -18.55 kcal/mol for AT and -23.42 kcal/mol for GC.