Synthesis, characterization, biological and theoretical studies of a new Pd(II) complex of drug carvedilol: Strong anticancer activity against several cell lines

Abstract

In this study, a new Pd(II) complex of the drug carvedilol (CAR), [Pd(CAR)2Cl2] (PdCAR), was synthesized and characterized using X-ray crystal structure determination, CHN elemental analysis, and FT-IR, 1H NMR and UV–Vis spectroscopies. The crystal structure of the above complex shows that the Pd atom lies on a center of symmetry and is coordinated by two ligands (CAR) and by two chloride anions in a square planar arrangement. It means that each carvedilol ligand is coordinating to the Pd atom in a monodentate fashion, via the aliphatic nitrogen atom. Theoretical studies showed that the nature of the bond between PdCl2 and two carvedilol ligands, similar to that between PdCl2 and two dimethylamine (DMA) ligands, is mainly electrostatic. Interestingly, the CAR−PdCl2 bond is stronger than the DMA−PdCl2 bond. The UV–Vis and NMR studies indicate that the PdCAR complex is stable in solution. The DNA interaction studies were performed using the molecular docking simulation. The results indicated that the binding affinity of the PdCAR for B-DNA is higher than that of the CAR. Furthermore, the cytotoxicity effects of CAR, PdCAR and cisplatin (CIS) against MCF-7, HepG2, SW-480, CT-26 and HEK-293 cell lines were also evaluated and compared by MTT assay. The results showed that the cytotoxicity of both CAR and PdCAR on the above cell lines in all cases, except MCF-7, is higher than that of CIS.