SYNTHESIS, IN SILICO STUDY AND CHOLINESTERASES INHIBITION ACTIVITY OF 2-SUBSTITUTED 2,3-DIHYDROQUINAZOLIN-4(1H)-ONE DERIVATIVES

We have synthesized and evaluated a number of 2,3-dihydroquinazolin-4(1H)-one derivatives as inhibitors of cholinesterases. In vitro assay results revealed that all synthesized compounds are active against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and few compounds having longer alkyl chain at C-2 position showed better inhibition activity than standard drug galantamine. Moreover, bromo derivatives 6a-d were more active than nitro 5a-d and their un-substituted counterparts 4a-d. Amongst all, compound 6d, with IC50 values of 4.8 +/- 1.01 mu M (AChE) and 11.1 +/- 1.15 mu M (BChE) can be considered as good cholinesterase (AChE/BChE), inhibitor with greater selectivity towards BChE. In silico calculations revealed that all compounds have good pharmacokinetic profile along with having high probabilities for penetration across blood brain barrier (BBB), human intestinal absorption (HIA), non-AMES toxicity and non-carcinogenicity except nitro substituted derivatives which were predicted to show AMES toxicity. The synthesized compounds may lead toward development of new potent cholinesterase inhibitors.