The effect of gallic acid on the copper(ii) complex of N-(methylpyridin-2-yl)-amidino-O-methylurea: crystal structure, DNA interactions, in vitro cytotoxicity and antibacterial activity

Abstract

A new copper(II) complex containing N-(methylpyridin-2-yl)-amidino-O-methylurea (L^3m) and gallic acid (HGA), [CuL^3m(HGA)]Cl₂ (1-HGA), was synthesized and characterized by elemental analysis and several spectroscopic methods. Crystallographic data of [CuL^3m(GA)]Cl·3H₂O revealed a distorted square planar geometry. Interactions with calf-thymus (CT) DNA were investigated by absorption titration, fluorescence spectroscopy, circular dichroism spectroscopy, viscosity measurements, gel electrophoresis and molecular docking. The binding constant (K_b) of 1-HGA was determined and found to be greater than that of the starting compound (1) with a non-intercalation mode. The in vitro cytotoxicity of 1-HGA against two human cancer cell lines (MCF-7 and HeLa) compared with normal (Vero) cells was determined by MTT assay. 1-HGA showed the best cytotoxicity toward MCF-7 (IC₅₀ 5.65 ± 1.29 μg mL⁻¹), being less than both 1 and cisplatin. The mechanism of cell death was further investigated by flow cytometry, and it was found that 1-HGA induces cell death through apoptosis in HeLa and MCF-7 during the S phase. The antibacterial activity of 1-HGA was also tested by the agar-well diffusion method against E. coli, Salmonella, and Campylobacter. 1-HGA was found to display the best antibacterial activities against all bacteria with a MIC of 0.78 μg mL⁻¹.