Novel 3,4-Dihydroxyphenyl-Thiazole-Coumarin Hybrid Compounds: Synthesis, In Silico and In Vitro Evaluation of Their Antioxidant Activity
Daniel Ungureanu,
Gabriel Marc,
Brîndușa Tiperciuc,
Cristina Moldovan,
Ioana Ionuț,
Anca Stana,
Ilioara Oniga,
Laurian Vlase,
Adrian Pîrnău,
Ovidiu Oniga
Affiliations
Daniel Ungureanu
Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Gabriel Marc
Department of Organic Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Brîndușa Tiperciuc
Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Cristina Moldovan
Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Ioana Ionuț
Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Anca Stana
Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Ilioara Oniga
Department of Pharmacognosy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 12 Ion Creangă Street, 400010 Cluj-Napoca, Romania
Laurian Vlase
Department of Pharmaceutical Technology and Biopharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Adrian Pîrnău
National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath Street, 400293 Cluj-Napoca, Romania
Ovidiu Oniga
Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
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.
