Design, synthesis, molecular docking, and some metabolic enzyme inhibition properties of novel quinazolinone derivatives

Abstract

3-Amino-2-ethylquinazolin-4(3H)-one (3) was synthesized in two steps from the reaction of amide (2), which was obtained from the treatment of methyl anthranilate (1) with propionyl chloride, with hydrazine. From the reaction of 3-amino-2-ethylquinazolin-4(3H)-one (3) with various aromatic aldehydes, novel benzylidenaminoquinazolin-4(3H)-one (3a-n) derivatives were synthesized. The structures of the novel molecules were characterized using infrared spectroscopy, nuclear magnetic resonance spectroscopy (H-1-NMR and C-13-NMR), and high-resolution mass spectroscopy. The novel compounds were tested against some metabolic enzymes, including alpha-glucosidase (alpha-Glu), acetylcholinesterase (AChE), and human carbonic anhydrases I and II (hCA I and II). The novel compounds showed K-i values in the range of 244-988 nM for hCA I, 194-900 nM for hCA II, 30-156 nM for AChE, and 215-625 nM for alpha-Glu. The binding affinities of the most active compounds were calculated as -7.636, -6.972, -10.080, and -8.486 kcal/mol for hCA I, hCA II, AChE, and alpha-Glu enzymes, respectively. The aromatic ring of the quinazoline moiety plays a critical role in the inhibition of the enzymes.