Discovery of New Hydrazone-Thiazole Polyphenolic Antioxidants through Computer-Aided Design and In Vitro Experimental Validation

Abstract

Oxidative stress is linked to a series of diseases; therefore, the development of efficient antioxidants might be beneficial in preventing or ameliorating these conditions. Based on the structure of a previously reported compound with good antioxidant properties and on computational studies, we designed several catechol derivatives with enhanced antioxidant potential. The compounds were synthesized and physicochemically characterized, and their antioxidant activity was assessed through different antiradical, electron transfer and metal ions chelation assays, their electrochemical behavior and cytotoxicity were studied. The results obtained in the in vitro experiments correlated very well with the in silico studies; all final compounds presented very good antioxidant properties, generally superior to those of the reference compounds used. Similarly, the results obtained from studying the compounds’ electrochemical behavior were in good agreement with the results of the antioxidant activity evaluation assays. Regarding the compounds’ cytotoxicity, compound 7b had a dose-dependent inhibitory effect against all cell lines. In conclusion, through computer-aided design, we developed several catechol thiazolyl-hydrazones with excellent antioxidant properties, of which compound 7b, with two catechol moieties in its structure, exhibited the best antioxidant activity.

Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects

“…Contrarily, mechanisms like single electron transfer–proton transfer (SET–PT) and sequential proton loss electron transfer (SPLET) are considered less favorable for phenolic compounds and were not evaluated in the present study [ 55 , 56 , 57 ]. The computations were conducted using Spartan20 (Wavefunction, CA, USA) on the B3LYP level of theory with the 6-311++G(d,p) basis set for compounds 1 – 6 in vacuum, a non-polar solvent and water, to obtain information regarding how the polarity of the solvent would influence the antioxidant activity of the compounds [ 55 , 58 , 59 ].…”

Combined Experimental and Theoretical Insights: Spectroscopic and Molecular Investigation of Polyphenols from Fagonia indica via DFT, UV–vis, and FT-IR Approaches

“…It is a highly reactive group and readily undergoes oxidative polymerization reactions to form complexes with other species. It exhibits strong antioxidant characteristics …”