Synthesis and molecular interaction study of a diphenolic hidrazinyl-thiazole compound with strong antioxidant and antiradical activity with HSA

Abstract

In this study we designed, synthesized and analyzed a water-soluble molecule presenting a good antioxidant and antiradical activity, namely Dihydroxy-Phenyl-Thiazol-Hydrazinium chloride (DPTH). This molecule contains 2’,4’-dihydroxyphenyl and the 2-hydrazinyl-4-methyl-thiazole fragments linked through a hydrazone and having very good antiradical scavenging, antioxidant activity and a low chelation activity in the in vitro evaluations. Knowing that, in the organism, the drugs are transported to the tissues generally bound to a plasma protein we, additionally, investigated its interaction with human serum albumin (HSA)-the main soluble protein in plasma capable of making complexes with various molecules, which deliver then, to the tissues. This binding can influence the pharmacokinetic and pharmacodynamic profile of drugs. Consequently, the interaction between DPTH and human serum albumin (HSA) was carefully examined using isothermal titration calorimetry (ITC) and T1 NMR selective relaxation time spectroscopy. According to ITC, DPTH: HSA interaction process was spontaneous and endothermic with an affinity constant Ka = 4.31 × 102 M−1 and the stoichiometry coefficient (n) was equal 1, which was subsequently confirmed by 1H NMR. Relaxation experiments provide quantitative information about the relationship between the binding affinity and structure of DPTH. Thus, association constant was determined as Ka = 9.65 × 102M −1. The results obtained by ITC and NMR were complemented with a molecular docking study.