Tokali_2023_Chem.Biodivers__e202301134

Novel quinazolinone derivatives (1-21) were synthesized from the reaction of acylated derivatives of 4-hydroxy benzaldehyde (AAD) with 3-amino-2-alkylquinazolin-4(3H)-ones (QD) with good yields (85-94%). The structures of the novel molecules were characterized using Fourier-transform Infrared (FTIR), Nuclear Magnetic Resonance (1H NMR - 13C NMR), and High-Resolution Mass Spectroscopy (HRMS). As the application of the synthesized compounds, their inhibition properties of the synthesized compounds on alpha-Glucosidase (alpha-Glu), Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and Carbonic anhydrase I-II (hCA I-II) metabolic enzymes were investigated. All compounds showed inhibition at nanomolar level with the Ki values in the range of 12.73+/-1.26 - 93.42+/-9.44 nM for AChE, 8.48+/-0.92 - 25.84+/-2.59 nM for BChE, 66.17+/-5.16 - 818.06+/-44.41 for alpha-Glu, 2.56+/-0.26 - 88.23+/-9.72 nM for hCA-I, and 1.68+/-0.14 - 85.43+/-7.41 nM for hCA-II. Molecular docking study was performed for understand the interactions of the most potent compounds with corresponding enzymes. Also, absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties of the compounds were investigated.