Design synthesis characterization and biological evaluation of some novel quinazoline derivatives for metabolic disorders

Abstract

A novel series of quinazolinone derivatives was designed based on literature review, basic chemistry principles and docking study using AutoDock software. All designed compounds with good docking score and inhibitory constant were checked for their Druglikeness and ADME properties using SwissADME web tool. They show good drug likeness properties, TPSA and absorption parameters and synthesis protocol of such selected targets of quinazolinone-4(3H)-one derivatives was achieved. newlineThis synthesis protocol includes a synthesis of benzamide derivatives from anthranilic acid using acid-amine reaction, followed by the cyclization using catalytic p-toluenesulfonicacid monohydrate and oxidation using (diacetoxyiodo)benzene to give bromo substituted quinazolin-4(3H)-ones, which were cross coupled to suitable boronic acid and alkyne derivatives using Suzuki-Miyaura and Sonogashira condition respectively with suitable catalyst, base and solvent system to afford corresponding 2, 3 and 6 substituted quinazolin-4(3H)-ones (GUNI-1 to GUNI-30) with moderate to high yields. newlineSynthesized compounds and key intermediates were characterized by FTIR, LC-MS, 1H-NMR and few with 13C-NMR analysis and their structure were confirmed as desired. newlineIn vitro biological evaluation was carried out for synthesized targets for anti-obesity and anti-diabetic activity using pancreatic lipase inhibition, alpha-amylase and alpha-glucosidase inhibition and non-enzymatic inhibition of haemoglobin glycosylation assay with reported methods and some compounds show good potential for ant-obesity and anti-inhibitory activity. newline newline