In vitro anticancer activities, multi-spectroscopic and in silico DNA binding studies of propranolol drug and its new Zn(II) complex

Abstract

A new Zn(II) complex of propranolol (PPN), [Zn2(PPN)2(μ-Cl)2] (ZnPPN), was synthesized and characterized using 1H NMR and FT-IR spectroscopies, CHN elemental analysis, cyclic voltammetry (CV) and conductance measurements. Then the interaction of both the drug and its Zn(II) complex with calf thymus DNA (ct-DNA) was studied using differential pulse voltammetry (DPV), multi-spectroscopic, and dynamic viscosity measurements, and also in silico simulations. The cytotoxicity studies against MCF-7 and HEK-293 cell lines were also evaluated and compared. DNA binding studies determined a higher affinity of ZnPPN for ct-DNA compared to the drug alone. Furthermore, the new ZnPPN complex was found as an intercalation binder of ct-DNA by competitive fluorescence and viscosity studies, while PPN binds to ct-DNA via a groove mechanism. Finally, experimental DNA binding and molecular docking studies are all well agreed with each other. The cytotoxicity studies showed that PPN, ZnPPN and cisplatin (CIS) have an IC50 value are 46.43 ± 7.23, 34.23 ± 8.52, 19.96 ± 6.89 µg/ml on MCF-7 cell line, respectively, and no cytotoxicity on the normal cell of HEK-293.