Carboxylate- and Sulfonate-Containing Quinazolin-4(3H)-one Rings: Synthesis, Characterization, and Carbonic Anhydrase I–II and Acetylcholinesterase Inhibition Properties

Abstract

Quinazolines are a group of bioactive heterocyclic compounds with a wide range of biological activities and have gained an important place in the design of active drugs with various targets due to their pharmacological properties. Carbonic anhydrase (CA) and acetylcholinesterase (AChE) inhibitors are very important pharmacologically. In this study, inhibition effects of newly synthesized quinazolin-4(3H)-one derivatives on human erythrocyte CA-I (hCA-I) and CA-II (hCA-II) isoenzyme and AChE activity were investigated. The structures of the novel compounds were characterized by fourier-transform infrared (FTIR), nuclear magnetic resonance (NMR), and high-resolution mass spectroscopy (HRMS). All molecules showed strong inhibitory effect in all three enzymes. 4-[(4-Oxo-2-(phenoxymethyl)quinazolin-3(4H)-ylimino)methyl]phenyl furan-2-carboxylate for hCA-I (IC50: 205 nM), 4-[(4-oxo-2-(phenoxymethyl)quinazolin-3(4H)-ylimino)methyl]phenyl isobutyrate for hCA-II (IC50: 209 nM), and 4-[(4-oxo-2-(phenoxymethyl)quinazolin-3(4H)-ylimino)methyl]phenyl propionate for AChE (IC50: 14.2 nM) were the molecules that showed the strongest inhibitory effect. Molecular docking studies were carried out to elucidate the possible interaction mechanism of the molecules in the active site of the enzymes. The affinity scores of the most active compounds for hCA-I, hCA-II, and AChE were determined as −134.765, −147.423, and −175.354 MolDock Score, respectively. © 2023 Wiley-VCH GmbH.