Synthesis, biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1H)-one derivatives as inhibitors of cholinesterases.

In search of potent inhibitors of cholinesterases, we have synthesized and evaluate a number of 2,3-dihydroquinazolin-4(1H)-one derivatives. The synthetic approach provided an efficient synthesis of the target molecules with excellent yield. All the tested compounds showed activity against both the enzymes in micromolar range. In many case, the inhibition of both enzymes are higher than or comparable to the standard drug galatamine. With the selectivity index of 2.3 for AChE, compound 5f can be considered as a potential lead compound with a feature of dual AChE/BChE inhibition with IC50 =1.6±0.10μM (AChE) and 3.7±0.18μM (BChE). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. The computed binding modes of these compounds in the active site of AChE and BChE provide an insight into the mechanism of inhibition of these two enzyme.