A biophysical insight into the mechanism of anticancer activity of salicylidene cyclohexanediamine based cobalt and nickel complexes through CT-DNA, BSA binding and docking study

Abstract

Two novel metal Schiff base complexes, [Co(L)(OH2)(Cl)].2DMF (1) and [Ni(L)].H2O (2) [H2L=N,N'-bis(5-bromo-3-(methoxy)salicylidene)cyclohexane-1,2-diamine] were prepared and structurally characterized through single crystal X-ray crystallography and usual spectroscopic techniques. The inhibitory action of H2L, 1 and 2 via MTT assay on MDA-MB 231, HCT-116, and A549 cell lines was assessed. The complexes exhibit lower IC50 values than the ligand (H2L> 2> 1). On the other hand, with normal human PBMC, they were found to be significantly nontoxic. The interaction of 1 and 2, with CT-DNA and serum albumin (BSA) through different biophysical experiments was checked to have a plausible understanding of their anticancer activity as well as pharmacological relevance. These investigations inferred that 1 had a greater affinity for CT-DNA and BSA than 2. 1 interacts with CT-DNA through intercalation whereas 2 exhibits a mixed mode of interaction (intercalation and groove binding). The complexes exhibit a predominantly hydrophobic interaction with BSA, which is static in nature and causes a prominent structural change of BSA, from α-helix to β-sheet. The rate of hydrolysis of the phospho-ester bond in PNPP was found to be four times faster with 1 than with 2. A molecular docking study was conducted to gain a deeper insight into the molecular interactions along with possible theoretical binding energies of the complexes with CT-DNA and BSA, and this was found to be in agreement with the experimental findings.