University of Khartoum

Identification of New Acetyl cholinesterase Inhibitors towards the Development of Anti-Alzheimer’s Agents

Identification of New Acetyl cholinesterase Inhibitors towards the Development of Anti-Alzheimer’s Agents

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Title: Identification of New Acetyl cholinesterase Inhibitors towards the Development of Anti-Alzheimer’s Agents
Author: Osman, Yossra Abdelmalik Mohamed
Abstract: Acetylcholinesterase (AChE) is the principle enzyme that terminates signalingat cholinergic synapses by rapid hydrolysis of neurotransmitter Acetylcholine (ACh). The development of effective new agents as AChE inhibitors is needed, which is the objective of the current study. Two hundred synthetic compounds obtained from Medicinal Biochemistry Laboratory Compounds Library at Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research were tested for their AChE inhibitory activity using in vitro AChE enzyme assay. In silico docking studies were carried out for the active compounds using Auto-dock and Surflex-dock software. Thirty three compounds were found to inhibit the AChE and their IC50 (concentration that inhibits the enzyme by 50%) values were calculated. Compounds showed best activity belong to xanthones and highest activity was obtained from compounds 3,6bis (3piperidin1ylmethoxy)-9H-xanthen-9-one and 3,6bis((4diethylamino)methoxy)-9H-xanthen- with IC50value 0.007μM followed by 3,6bis(5pyrrolidin-1-ylmethoxy)-9H-xanthen-9-one with IC50value 0.009μM, 3,6-bis(3pyrrolidin-1-ylmethoxy)-9H-xanthen-9-one with IC50value 0.012μM and 3,6bis(3morpholinomethoxy)-9H-xanthen-9-one with IC50 value 0.029μM respectively. Compounds belong to chalcones group showed also interesting activity but with IC50 values (IC50 22-37μM) higher than those obtained from xanthones compounds. Carbamates and benzenesulfonamides compounds showed less AChE inhibitory activity (IC50 values >50μM). In silico docking studies were carried out for the active compounds using Auto-dock and Surflex-dock software to predict the molecular interactions between the compounds and the AChE enzyme, and their binding pattern within the active site. Results obtained highly confirmed the in vitro studies, and thus, these active compounds were suggested to be interesting lead new AChE inhibitors.
URI: http://khartoumspace.uofk.edu/123456789/24665


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