title: An Efficient Synthesis of bi-Aryl Pyrimidine Heterocycles: Potential New Drug Candidates to Treat Alzheimer's Disease.
abstract: A series of 13 novel pyrimidine-based sulfonamides 6a-m were synthesized in short periods of time under microwave conditions in good to excellent yield (54-86%). The chemical structures of these heterocycles consist of a central pyrimidine ring having a phenyl group and pyrimidine groups with sulfonamide motifs. The enzyme inhibitory potential of these compounds was investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) because these enzymes play a crucial role in the treatment of Alzheimer's disease. As compared to the reference compound eserine (IC50= 0.04 ± 0.0001 μM for AChE and IC50= 0.85 ± 0.0001 μM for BChE), the IC50values of the synthesized compounds ranged from 3.73 ± 0.61 μM to 57.36 ± 0.22 μM for AChE and 4.81 ± 0.16 μM to 111.61 ± 0.53 μM for BChE. Among these tested compounds, 6j having a -CH3group was found to be the most potent one against both enzymes (AChE, IC50= 3.73 ± 0.61 μM; BChE, IC50= 4.81 ± 0.16 μM). Quantitative structure-activity relationship (QSAR) and molecular docking studies of the synthesized compounds were also performed.
authors.affiliation: Department of Chemistry, GC University, Lahore, Pakistan.
authors.forename: Tanzeel Ur
authors.initials: TU
authors.lastname: Rehman
authors.affiliation: Department of Chemistry, GC University, Lahore, Pakistan.
authors.forename: Islam Ullah
authors.initials: IU
authors.lastname: Khan
authors.affiliation: Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, UAE.
authors.forename: Hamadeh
authors.initials: H
authors.lastname: Tarazi
authors.affiliation: Department of Chemistry, GC University, Lahore, Pakistan.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Riaz
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yar
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008872:Microwaves; D008958:Models, Molecular; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D006571:Heterocyclic Compounds; D011743:Pyrimidines; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C030986:pyrimidine
keywords: AChE; Alzheimer's disease; BChE; Pyridine; Pyrimidines; Sulfonamides