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

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.

Automated summary

Oxidative stress is associated with various diseases, and developing efficient antioxidants could be beneficial in preventing or improving these conditions. By utilizing structure optimization and computational studies, we designed several catechol derivatives with enhanced antioxidant potential. These compounds were synthesized, characterized, and evaluated for their antioxidant activity through various tests. The results showed that the final compounds had excellent antioxidant properties, consistently outperforming the reference compounds. Additionally, the compounds' electrochemical behavior and cytotoxicity were also studied and correlated well with the antioxidant activity. Compound 7b, with two catechol moieties in its structure, exhibited the highest antioxidant activity.