Molecular docking and inhibitory effects of a novel cytotoxic agent with bovine liver catalase

Abstract

The synthesis of new metal complexes with fewer side effects than old drugs, such as cisplatin, is the major research pathway of many scientists. In this regard, the study of interactions between the promising complexes and certain targets such as enzymes is necessary. In this work, we reported the synthesis of Zn(II) complex of a novel bidentate Schiff base ligand, SBL, obtained from the condensation of 1-(2-aminoethyl)piperazine and 2,3-butanedione monoxime. The anticancer activities of [Zn(SBL)2]Cl2 complex against HT-116 cancer cell lines were studied by MTT assay and revealed that this complex can induce the cytotoxicity in the human colon cancer cell. The side effects of the prepared complex on the structure and catalytic function of bovine liver catalase (BLC) were evaluated by various spectroscopic and theoretical methods. The enzyme inhibition kinetics showed that Zn(II) complex inhibited catalase function by mixed-type inhibition. UV–Vis spectra, CD spectroscopy, synchronous, and 3D fluorescence confirmed the conformational changes in the structure of BLC in the presence of Zn complex. The fluorescence measurements showed that this complex quenches the intrinsic fluorescence of BLC via static quenching mechanism. The values of binding constants were obtained 2.68 × 104 M−1 and 0.48 × 104 M−1 at 300 and 310 K, respectively. The thermodynamic parameters revealed that the reaction of Zn(II) complex with catalase could proceed spontaneously through van der Waals forces and hydrogen bonds. The molecular docking simulation in the well coherent with kinetics results showed that there is one binding site for Zn(II) complex on BLC and this complex did not directly bind to the catalase active site.