Novel 3,4-Dihydroxyphenyl-Thiazole-Coumarin Hybrid Compounds: Synthesis, In Silico and In Vitro Evaluation of Their...

Oxidative stress represents a key process in many physiopathological mechanisms involved in several diseases. Therefore, antioxidants represent an important strategy in reversing this pathologic process. In the present study, we proposed the design, synthesis, computational, and in vitro evaluation of seven novel hydroxyphenyl-thiazole-coumarin hybrid compounds (4a-g) as antioxidant molecules. The conducted theoretical quantum and thermodynamical calculations revealed compound 4f as the most promising antioxidant, having the highest HOMO-LUMO gaps (3.13 eV in vacuum, 3.22 eV in nonpolar environment, and 3.33 in water) and some of the lowest BDE values (68.23 kcal/mol and 69.63 kcal/mol for O-H and N-H bonds in nonpolar environment). This was transposed in the results obtained following the in vitro antiradical (DPPH^• and ABTS^•+) and electron transfer capacity assays (TAC, RP, FRAP, and CUPRAC), although all compounds showed important antioxidant activity, superior in almost all instances to ascorbic acid and Trolox, which were used as references. Compounds 4f and 4g can serve as molecules for further research involving in vivo antioxidant activity and possible synergistic mechanisms.