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Synthesis and biological evaluation of new oxopyrrolidine derivatives as inhibitors of acetyl cholinesterase and β amyloid protein as anti – Alzheimer’s agents
Institution:1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;2. Biochemistry Department, Cairo General Hospital, Egypt;3. Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;1. Genetics Laboratory, Forest Research Institute Malaysia, 52109 Kepong, Selangor, Malaysia;2. Biological Resources Programme, Forest Research Institute Malaysia, 52109 Kepong, Selangor, Malaysia;1. Department of Chemical and Environmental Engineering, University of Arizona, P.O. Box 210011, Tucson, AZ 85721-0011, USA;2. Departamento de Procesos y Tecnología, División de Ciencias Naturales e Ingeniería, Universidad Autónoma Metropolitana – Unidad Cuajimalpa (UAM-C), Vasco de Quiroga 4871, Col. Santa Fe Cuajimalpa, Cuajimalpa de Morelos, C.P. 05300 México, D.F., Mexico;3. Department of Chemistry & Biochemistry, University of Arizona, P.O. Box 210041, Tucson, AZ 85721-0041, USA;4. Department of Soil, Water & Environmental Science, University of Arizona, P.O. Box 210038, Tucson, AZ 85721-0038, USA;1. Department of Physics, Vytautas Magnus University, Kaunas, Lithuania;2. Centre for Hydrogen Energy Technologies, Lithuanian Energy Institute, Kaunas, Lithuania;1. Department of Medical Biology, Medical University of Warsaw, Nowogrodzka 73, 02-018, Warsaw, Poland;2. Coridon Pty Ltd, Research Wing, Princess Alexandra Hospital, Ipswich Road, Buranda, QLD 4102, Australia;3. Faculty of Agriculture and Life Sciences, PO Box 84, Lincoln University, Canterbury, New Zealand;4. Probe International Inc., Auckland, New Zealand;5. Department of Microbiology, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-952 Gdansk, Poland;1. Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt;2. Chemistry Department, Faculty of Science, Kafrelsheikh University, Kafrelsheikh, Egypt
Abstract:A new series of oxopyrrolidines was synthesized and evaluated for their effect on Alzheimer‘s disease by measuring their inhibitory activity against acetyl cholinesterase enzyme and amyloid β 42 protein. Most of the compounds showed good inhibitory activity with ethyl 2-(2-(2, 6-dimethylphenylcarbamoyl)- 5-oxopyrrolidin-1-yl) acetate (V) having the highest activity against acetyl cholinesterase with IC50 value 1.84 ng/g tissue compared to standard donepezil 3.34 ng/g tissue. Furthermore, compound 1-((4-(4-chlorophenyl) piperazin-1-yl) methyl)-N-(2,6-dimethylphenyl)-5- oxopyrrolidine- 2-carboxamide (IIIe) displayed the highest activity against β 42 protein with IC50 value of 11.3 Pg/g tissue compared to 18.4 Pg/g tissue of donepezil.
Keywords:Oxopyrrolidine  Donepezil  Synthesis  Acetylcholinesterase  Amyloid protein  RRXSJRPESHKGNC-IONKJSKOSA-N  IIRVXERVECMIQO-FSLXUQCTSA-N  WAYFMFWPRDBHGH-TXPJLPQESA-N
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