Synthesis, biological activities of chalcones and novel 4-acetylpyridine oximes, molecular docking of the synthesized products as acetylcholinesterase ligands

Abstract

Heterocyclic chalcones were synthesized by reaction of 4-acetylpyridine with the corresponding aromatic aldehydes under Claisen Schmidt conditions. These chalcones were used as starting material for the synthesis of oximes in the presence of hydroxylamine hydrochloride. The structures of the synthesized compounds were confirmed by IR, 1H NMR, 13C NMR and ESI-MS, HRMS spectral analyses. All the synthesized compounds were evaluated for their antioxidant activity by DPPH• method and their in vitro antimicrobial activity by disk diffusion method against two Gram-negative bacteria, one Gram-positive bacteria and two fungal strains (C. albicans and A. niger). The results showed that the synthesized compounds did not display significant antioxidant activity. However, compounds 3b, 3d, 3f, 3h, 3i showed excellent antibacterial activity better than the standard drug against the bacterial strain S. aureus (ATCC 25923). The two compounds 3c, 3d proved very active against the fungal strain A. niger (MIC= 7.81 µg/ mL, 15.62 µg/mL respectively) while the antifungal drug used as reference (Fluconazole) was inactive. Molecular docking and molecular dynamics results revealed that the synthesized compounds, 4e, 4c, and 5j, were involved in a large number of favorable interactions with the active site residues of the acetylcholinesterase protein, which can stabilize the ligands in the active site and increase their affinities.