Synthesis, biological evaluation, and molecular docking of novel quinazoline derivatives as multifunctional bioactive agents.

In this study, a new series of 1,2-dihydroquinazoline and quinazoline derivatives was synthesized via an efficient one-pot multicomponent reaction between 2-aminobenzophenone, various aromatic or heteroaromatic aldehydes, and ammonium acetate, using DABCO as an organocatalyst in ethanol under mild conditions. The structures of the synthesized compounds were confirmed by spectroscopic techniques including 1H NMR, 13C NMR, HRMS, and, in selected cases, X-ray crystallography. The antioxidant potential of the compounds was evaluated using four complementary in vitro assays: DPPH, ABTS, ferric-phenanthroline, and reducing power methods. Several 1,2-dihydroquinazoline derivatives showed notable radical scavenging activity, particularly compounds 4d and 4c, with IC₅₀ values comparable to standard antioxidants (BHT and BHA). Moreover, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were assessed using Ellman's method. Some derivatives such as 5d and 4f exhibited potent AChE inhibition, surpassing galantamine in activity, while others like 4b showed strong BChE inhibition. Antibacterial screening against Gram-positive and Gram-negative strains revealed moderate to good activity, especially for compounds 4b, 4d, and 4f. Molecular docking studies were performed to investigate the binding modes of the most active compounds within AChE and BChE active sites, supporting the experimental findings and providing insights into structure-activity relationships. These results highlight the potential of the synthesized quinazoline-based scaffolds as multifunctional bioactive agents.