Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma, Alzheimer's Disease and Diabetes Mellitus

Abstract

Quinazolinones, which represent an important part of nitrogen-containing six-membered heterocyclic compounds, are frequently used in drug design due to their wide biological activity properties. Therefore, the novel quinazolinones were synthesized from the reaction of acylated derivatives of 4-hydroxy benzaldehyde with 3-amino-2-alkylquinazolin-4(3H)-ones with good yields (85-94%) and their structures were characterized using Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (H-1-NMR, C-13-NMR), and High-Resolution Mass Spectroscopy (HR-MS). 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 K-i 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 to 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.