Title: Synthesis, Characterization of Pyrano-[2,3-c]-Pyrazoles Derivatives and Determination of Their Antioxidant Activities

Background: Antioxidants are developed to assist the immune system and overcome oxidative stress, the aggression of cellular constituents due to imbalance between reactive oxygen species and the inner antioxidant system. The main objective of this study was to search for new and potent antioxidants to protect humans against diseases associated with oxidative stress. Methods: In this study, three pyrano-[2,3-c]-pyrazole derivatives were synthesized via multicomponent reaction (MCR) approach and were characterized, using a melting point, HPLC, and spectroscopic analyses (IR; 1H-NMR; 13C-NMR). All of the generated compounds were screened for their antioxidant properties in-vivo, using ciliate “Tetrahymena” as a model organism exposed to oxidative and nitrative stress. They were then studied in vitro by computer modelling, i.e., in silico, using “Autodock” software to stimulate the docking processes. Results: The results demonstrated that the three compounds (5a, b, c) are biologically active and possess potent antioxidant activities, especially the 5a and 5b derivatives. On the other hand, the in vitro bioassays revealed that the 5a derivative possessed a significant antioxidant activity much greater than ascorbic acid. Accordingly, the in silico data are consistent with the experimental data. Conclusions: These findings confirmed the potent antioxidant property of the synthesized compounds, providing us with new inspiration and challenges to design a library of pharmaceutical compounds with strong activity and low toxicity in the future.