title: Design and discovery of Novel Thiazole acetamide derivatives as anticholinesterase agent for possible role in the management of Alzheimer's.
abstract: A novel series of thiazole acetamides was synthesized in excellent yields and characterized with the aid of various spectroscopic and elemental analysis. These compounds were evaluated for in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities for possible benefit in Alzheimers disease (AD). Among the synthesized compound, 6d was identified as the most potent compound of AChE (IC50=3.14±0.16 μM) with a selectivity index (SI) of 2.94 against BuChE. These compounds were further tested for inhibition of Aβ aggregation and β-secretase, where it showed potent inhibition which confirmed its multifactorial benefits in AD. The toxicity and docking study were also carried out to exemplify the pharmacological profile of compound 6d as prospective lead molecule against AD.
authors.affiliation: Department of Internal Neurology, Linyi People's Hospital, No. 27, Jiefang Road, Linyi, Shandong 276000, PR China.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Sun
authors.affiliation: Department of Internal Neurology, Linyi People's Hospital, No. 27, Jiefang Road, Linyi, Shandong 276000, PR China.
authors.forename: Li-Xiang
authors.initials: LX
authors.lastname: Tu
authors.affiliation: Department of Internal Neurology, Linyi People's Hospital, No. 27, Jiefang Road, Linyi, Shandong 276000, PR China.
authors.forename: Feng-Juan
authors.initials: FJ
authors.lastname: Zhuo
authors.affiliation: Department of Internal Neurology, Linyi People's Hospital, No. 27, Jiefang Road, Linyi, Shandong 276000, PR China. Electronic address: liusongxia@hotmail.com.
authors.forename: Song-Xia
authors.initials: SX
authors.lastname: Liu
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D000081:Acetamides; D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D013844:Thiazoles; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D053829:Amyloid Precursor Protein Secretases
keywords: Acetylcholinesterase; Docking; Synthesis; Thiazole acetamides