In silico Investigations, Design and Synthesis of Some Novel Quinazolinone Derivatives

The present research has been focused on designing and synthesizing new derivatives of quinazolinone heterocycle.The designed derivatives were subjected to in silico investigations by conducting PASS studies in which novel predicted antiviral activity of this heterocycle against picornavirus was explored.These designed derivatives were also subjected to in silico toxicity risk assessment studies using Osiris property explorer in which toxicities viz., mutagenicity, tumorigenicity, carcinogenicity and irritability were predicted and prediction of properties viz., c logP, solubility, mol weight and drug score was also done.All the compounds were found to be devoid of any predicted toxicities with predicted properties in acceptable range.Hence, they were further subjected to docking studies where interaction with protein 4CTG identified as target for the antiviral (Picornavirus) activity was studied.The docking results were found to be comparable to that of the parent quinazolinone molecule.Hence, the designed quinazolinone derivatives were further subjected to wet-lab synthesis.The compounds were recrystallized and subjected to structure elucidation studies by IR spectroscopy.As these derivatives of quinazolinone have shown promising results in docking, with compounds 2a, 2b and 2c showing optimum binding affinity of -8.0 kcal/mol, -8.1 kcal/mol and -8.2 kcal/mol; respectively which is better than that shown by parent compound showing binding affinity of -7.1 kcal/mol to the target protein 4CTG.Conclusively, it can be surmised that these synthesized compounds can be further subjected to in vitro and in vivo biological screening against Picornavirus.