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

Abstract

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 IC=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.

2,3-Dihydroquinazolin-4(1H)-one as a privileged scaffold in drug design

“…HCl in EtOH 14 or in association with concentrated HNO 3 (ref. 16) was used as catalyst under reux conditions. As reported, DHQ derivatives were oen synthesized in the presence of a catalytic amount of H 2 SO 4 (ref.…”

Tris-diamine-derived transition metal complexes of flurbiprofen as cholinesterase inhibitors

“…Standard colorimetric procedures were used in assaying the inhibitory activities of the complexes [16,19].…”

“…In the present study which is a continuation of the search for new potent cholinesterase inhibitors [16], and keeping in view the cholinesterase inhibitory properties of NSAIDsdiamines, a relatively new class of flurbiprofen and its transition metal complexes with diamines (1,2-diaminoethane and 1,3-diaminopropane) was introduced as anti-cholinesterase inhibitors.…”

Experimental and Theoretical Approaches in the Study of Phenanthroline‐Tetrahydroquinolines for Alzheimer's Disease

“…[13a,15] In this field, recent studies designed and synthesized dihydropyrimidine and quinazoline bicycle as selective inhibitors against AChE enzyme. [16] Likewise, quinolinyl chalcones derivatives exhibited selective inhibition for BChE enzyme displayed significant inhibition for AChE, [17] Similarly, cumarine-quinolines compounds showed ACHE selective inhibition. [15d] The change of functional groups in basic structure demonstrated variance in inhibition potential against BChE and AChE.…”