Electrochemical and spectroscopic investigations of isoniazide and its analogs with ds.DNA at physiological pH: Evaluation of biological activities

Abstract

Interaction and binding of isonicotinic acid hydrazide (INH) and its two analogs; pyrazine carboxylic acid hydrazide (PCH) and 2,4-dihydroxy benzoic acid hydrazide (2,4-DHBAH) with DNA has been investigated by UV-spectroscopy and cyclic voltammetry (CV) at physiological conditions of pH and temperature. Experimental results from both techniques were in good agreement and indicated stronger binding and formation of hydrazides–DNA complexes via intercalation. Among three hydrazides, 2,4-DHBAH showed greater interaction toward DNA at stomach pH (4.7) as evident from its comparatively greater binding constant, { K b ; 2.02 × 10 4 M −1 (UV), 3.13 × 10 4 M −1 (CV)}. The greater binding site size ( n = 3) for 2,4-DHBAH at stomach pH inferred 3:1 binding stoichiometry and possibility of electrostatic interactions or hydrogen bonding along with intercalative mode of interaction between 2,4-DHBAH and DNA. The free energies of hydrazides–DNA complexes indicated the spontaneity of their binding. 2,4-DHBAH has shown promising anti-bacterial activities while anti-oxidant and cytotoxic potentials were exhibited by all three hydrazides.