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

•Aromatic chalcones serve as the fundamental building block of numerous crucial biological compounds, and the feature of skeletal modification to produce a new class of organic heterocyclic compounds.•Michael's addition reaction is the most significant carbon-carbon bond-forming in organic synthesis, numerous medicines are considered to be anti-carcinogens and anti-inflammatory are connected via Michael's addition reaction.•Derivatives of cyclohexenone are formed by cyclo-condensation of chalcones and ethyl acetoacetate, under the influence of NaOH, the presence of active groups linked to the cyclohexenone ring is responsible for the excellent anticancer and antibacterial activities. 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. [Display omitted]