 Chalcone 3 was subjected to pressure microwave irradiation to produce various derivatives, including 2-hydroxyphenyl cyanopyridone, 2-hydroxyphenyl acetylcyclohexanone, thiono, 2, 3, C, chromin 4-1, and chromin 4-1. The synth-sized compounds were characterized by FTIR, 1-HNMR, 13-CNMR, and mass spectra. Additionally, the antioxidant activity of Compound 12 was evaluated against two proteins, PDBID, 1-DH2 and PDBID, 3-RP8, and compared to ascorbic acid. Compound 12 was also optimized through DFT, B3-LYP, 6-31G, D, P, basis set and identified through X-ray single crystal diffraction with Hirschfield analysis. This article was authored by Mona A. Chalabi, Asma M. Fahim, and Sameh A. Rizik.