In vitro antioxidant activity of nicotinic acid hydrazides: experimental and theoretical study Scientific paper

Abstract

The formation of reactive oxygen species (ROS) in the human body can lead to cell damage. Despite the body's natural defences, including the enzyme superoxide dismutase, novel antioxidant small molecules are needed.  In this work, in vitro antioxidant activity of seven nicotinic acid amides (NcAs) derived from nicotinic acid and mono-thiocarbohydrazones was investigated using DPPH, ABTS, CUPRAC, and TAC assays. The compounds exhibited IC₅₀ values between 0.202 to 1.297 mM in the DPPH assay, which improved to 0.114-0.638 mM upon the addition of water in the system. In the ABTS assay, IC₅₀ values ranged from 0.107 to 0.365 mM. CUPRAC and FRAP assays indicated reducing antioxidant power of 1.973-4.650 and 1.564-3.472 mM L^-1, respectively. Moderate antioxidant activity was also observed in the phosphomolybdenum assay for total antioxidant capacity. The density functional theory calculations revealed that the S-H bond of thioenol 1 tautomer, with a low bond dissociation enthalpy (BDE) of around 270 kJ mol^-1, is the favourable site for hydrogen atom transfer (HAT) to reactive free radicals. Additionally, all compounds exhibited high stability constants with Fe²⁺ and Fe³⁺ ions (K_s ~10⁸), forming complexes with ML stoichiometry.