title: Synthesis, biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1H)-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 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.
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Sarfraz
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha, Pakistan.
authors.forename: Nargis
authors.initials: N
authors.lastname: Sultana
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: umerrashid@ciit.net.pk.
authors.forename: Umer
authors.initials: U
authors.lastname: Rashid
authors.affiliation: School of Science & Engineering, Teesside University, Tees Valley, Middlesbrough TS1 3BA, UK.
authors.forename: Muhammad Safwan
authors.initials: MS
authors.lastname: Akram
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara 18000, Dir (L), Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Sadiq
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha, Pakistan. Electronic address: tariqmi2000@yahoo.com.
authors.forename: Muhammad Ilyas
authors.initials: MI
authors.lastname: Tariq
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004593:Electrophorus; D006736:Horses; D006801:Humans; D062105:Molecular Docking Simulation; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D052999:Quinazolinones; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: 2,3-Dihydroquinazolin-4(1H)-one; Alzheimer’s disease; Cholinesterases; Dual inhibitors