Two new cyclohexenone derivatives: Synthesis, DFT estimation, biological activities and molecular docking study

Abstract

Two new cyclohexenone carboxylate derivatives (6a-b) were synthesized through an additional ring-forming chalcone. FT-IR, 1H, 13C NMR, and Mass spectroscopy techniques confirmed the skeletons. The antibacterial, antioxidant, and colon cancer HT-29 cell activity of synthetic substances were assessed. Compound 6a's IC50 is 23.95 and 60.28 for its antioxidant and anticancer activities, whereas Compound 6b's IC50 is 27.56 and 62.72, respectively. MIC values for compound 6a are 15.75 ± 1.12, 10.25 ± 1.27, and 65.61 ± 1.72 against Staphylococcus aureus, Escherichia coli bacterial strains, and Candida albicans, respectively, whereas for compound 6b is equal to 18.32 ± 1.53, 12.63 ± 1.36, and 78.91 ± 1.94. Based on the extent of (B3LYP) and a 6-31G (d, p) basis set, the HOMO and LUMO of synthesized compounds were computed using the density functional theory (DFT) method. Energy gaps for products 6a and 6b are 2.8272 and 2.3360, respectively. Docked products had binding affinities of −9.5 and −9.1 for compounds 6a and 6b, respectively, with the crystal structure of recombinant human acetylcholinesterase in complex with donepezil (PDB ID: 4ey7). Consequently, according to experimental and computational studies, compound 6a is more active than compound 6b.