Synthesis of derivatives of cleistopholine and their anti-acetylcholinesterase and anti-β-amyloid aggregation activity |
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| Institution: | 1. Provincial Key Laboratory of Pharmaceutics in Guizhou Province, Guizhou Medical University, Beijing Road, Guiyang 550004, China;2. School of Pharmacy, Guizhou Medical University, 4 Beijing Road, Guiyang 550004, China;3. National Engineering Research Center of Miao’s Medicines, 4 Beijing Road, Guiyang 550004, China;4. College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, China;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. Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife 220005, Osun State, Nigeria;2. Drug Research and Production Unit, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife 220005, Osun State, Nigeria;3. Department of Pharmaceutics, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife 220005, Osun State, Nigeria;4. Department of Biochemistry, Faculty of Science, Obafemi Awolowo University, Ile-Ife 220005, Osun State, Nigeria;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife 220005, Osun State, Nigeria;1. Centre for Advanced Drug Research, COMSATS Institute of Information Technology, 22060 Abbottabad, Pakistan;2. Department of Chemistry, Quaid-I-Azam University, 45320 Islamabad, Pakistan;3. Département de microbiologie-infectiologie et d''immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada;4. Centre de Recherche du CHU de Québec – Université Laval, Québec, QC, Canada;1. Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;2. Department of Biomedical and Forensic Sciences, University of Cape Coast, Cape Coast, Ghana |
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| Abstract: | A series of 6- and 9-substituted cleistopholine derivatives has been designed, synthesized and investigated to inhibit the aggregation of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-myloid (A β). Results showed that these synthetic compounds had excellent AChE inhibitory activity and a significant in vitro inhibitory potency toward the self-induced A β aggregation. When SH-SY5Y cells were treated with these substituted cleistopholine derivatives during they overexpressed the Swedish mutant form of human β -amyloid precursor protein (APPsw), A β 42 secretion levels were significantly reduced. According to a parallel artificial membrane permeation assay for BBB, seven out of these sixteen synthetic compounds probably could cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS). |
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| Keywords: | Cleistopholine derivative Synthesis Cholinesterase inhibitor β-Amyloid aggregation |
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