The new metal-based compound from anticancer drug cytarabine: Spectral, electrochemical, DNA-binding, antiproliferative effect and in silico studies

Within the scope of this study, new dimeric zinc(II)-based analog of Cytarabine (Cyt) (an anticancer drug) was synthesized by considering different analytical conditions and characterized using analytical and spectroscopic methods. The proposed structure of this dimeric metal-based compound was characterized as Zn₂(Cyt)₂Cl₄. Geometry optimizations of the compound were performed in a vacuum without any symmetry constraints at density functional theory (DFT) level using the Gaussian 09 package program. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) have been given a DFT calculation section. Thermal behavior of the compound was investigated by thermal gravimetric analysis (TGA) and differential thermal analysis (DTA) techniques. This compound was transformed into metal oxides after thermal degradation. The electrochemical properties of both ligand and Zn₂(Cyt)₂Cl₄ were analyzed by Cyclic Voltammetry (CV) using glassy carbon electrode at different pH values. Also, the interactions of Cyt and Zn₂(Cyt)₂Cl₄ compound with fish sperm double strain deoxyribonucleic acid (FSdsDNA) were investigated by measuring their binding constant (K_b) to FSdsDNA. The results showed that Cyt and Zn₂(Cyt)₂Cl₄ metal-based compound could bind to FSdsDNA through groove-binding mode into the DNA helix. The antiproliferative activities of Cyt and the obtained new metal-based compound were investigated using three different concentrations on the HeLa cell line and the obtained values were compared with the commercially available metal-based drugs cisplatin, oxaliplatin, and carboplatin.