Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma, Alzheimer's Disease and Diabetes Mellitus
Feyzi Sinan Tokalı, Parham Taslımı, Burak Tüzün, Ahmet KARAKUŞ, Nastaran Sadeghian, İlhami Gülçın
Abstract
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 ( 1 H‐NMR, 13 C‐NMR), and High‐Resolution Mass Spectroscopy (HR‐MS). As the application of the synthesized compounds, their inhibition properties of the synthesized compounds on α‐Glucosidase (α‐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 α‐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.