A comprehensive study of nitroxoline - Ct-DNA interaction using electrochemical, spectroscopic, viscometry and thermodynamics as analytical tools

Abstract

Nitroxoline (NXN) is an antibiotic of nitroquinoline family which is used for the treatment of urinary tract infections and as a biofilm eradicating agent. Since it shows potential antitumor activity, it is also considered a promising candidate for repurposing in cancer treatment. Present article reports on electrochemical investigations of nitroxoline, its interaction with ct-DNA using cyclic voltammetry, UV-visible spectroscopy, viscometry, molecular modelling, and thermodynamics as analytical tools. An irreversible reduction peak is observed at about -0.45 V at pH 4.0 which shifts to more negative potentials with increasing scan rate. With the addition of DNA, the signal intensity decreases indicating formation of an adduct which enabled calculation of binding constant K_b = (9.175±0.728) × 10⁴ M^-1 and 2S = (0.925±0.150). Spectroscopic measurements yielded a value of (3.366±0.0.193) × 10⁴ M^-1. Viscosity measurements show intercalation binding mode for the drug which is supported by preliminary molecular docking studies. Thermodynamic studies reveal that ∆G° is negative and both ∆H° and ∆S° are positive, indicating spontaneity of the binding process and hydrophobic forces are dominant in binding of the drug. Electrochemical parameters, transfer coefficient (α), diffusion coefficient (D₀) and heterogeneous electron transfer rate (k_s,h) obtained for nitroxoline at pH 4.0 indicate mild electron transfer kinetics. Quinoline structure and nitro group are medicinally important. Present study reports for the first time qualitative and quantitative data on an important member of the quinoline family which would be of interest to researchers engaged in drug development.

Keywords: Binding mode; Ds-DNA; Molecular docking; Nitroxoline; Thermodynamic parameters.