Synthesis, x-rays analysis, docking study and cholinesterase inhibition activity of 2,3-dihydroquinazolin-4(1H)-one derivatives

Document Type: Research Article


1 Department of Chemistry, University of Sargodha, Sargodha, PAKISTAN

2 Department of Chemistry, COMSATS University, Abbottabad Campus, PAKISTAN


In search of potent cholinesterase inhibitors, we have carried out synthesis and biologically evaluation of various benzaldehyde based 2,3-dihydroquinazolin-4(1H)-one derivatives. In vitro assay results revealed that all the synthesized compounds showed activity against both enzymes (AChE and BChE) and in few cases, the inhibition activity was even higher than or comparable to the standard drug galantamine. Overall, compounds having chloro or methoxy group attached to para position of benzaldehyde resulted potent cholinesterase inhibitors. Within the series, bromo derivatives 4a-i were more active than their un-substituted counterparts. Amongst all, compound 4c (6,8-dibromo-2-(3-bromo-4-chloro-phenyl)-2,3-dihydro-1H-quinazolin-4-one) with selectivity index of 3.7 for AChE, displayed IC50 values of 3.7±1.05 µM (AChE) and 13.7±0.64 µM (BChE) and can be considered as potential lead compound with a feature of dual cholinesterase (AChE/BChE) inhibition. Insight into mechanism of inhibition of the synthesized compounds was provided by computed binding modes in the active site of AChE and BChE. Docking study on both isomers of the quinazoline also supported in vitro assay results. Preliminary in silico studies by using online admetSAR server showed that all compounds possessed good pharmacokinetic profile except nitro and methoxy substituted derivatives which were predicted to exhibit AMES toxicity. The synthesized compounds can be used as structural foundation for the preparation of new potent cholinesterase inhibitors.


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