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

• DOI: 10.1016/j.ejmech.2011.11.014
• Publication Date: 2011-11-19T08:12:43Z
• Authors: Nasima Arshad; Uzma Yunus; Shumaila Razzque; Maliha Khan; Samreen Saleem; Bushra Mirza; Naghmana Rashid
• Keywords: Binding Sites; Hydroxyl Radical; Spectrum Analysis; Temperature; DNA; Free Radical Scavengers; Hydrogen-Ion Concentration; 01 natural sciences; Anti-Bacterial Agents; 0104 chemical sciences; 3. Good health; Oxidative Stress; Hydrazines; Pyrazines; Electrochemistry; Isoniazid; Animals; DNA Damage

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.