Synthesis of aminoalkyl-substituted coumarin derivatives as acetylcholinesterase inhibitors.
Alzheimer's disease, one of the most common forms of dementia, is a progressive neurodegenerative disorder symptomatically characterized by declines in memory and cognitive abilities. To date, the successful therapeutic strategy to treat AD is maintaining levels of acetylcholine by inhibiting acetylcholinesterase (AChE). In the present study, coumarin derivatives were designed and synthesized as AChE inhibitors based on the lead structure of scopoletin. Of those synthesized, pyrrolidine-substituted coumarins 3b and 3f showed ca. 160-fold higher AChE inhibitory activities than scopoletin. These compounds also ameliorated scopolamine-induced memory deficit in mice when administered orally at the dose of 1 and 2 mg/kg.
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
Seung Ok
SO
Nam
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
Dong Hyun
DH
Park
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
Young Hun
YH
Lee
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Oriental Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Republic of Korea.
Jong Hoon
JH
Ryu
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Medicinal Chemistry Laboratory, Department of Pharmacy, College of Pharmacy, Kyung Hee University, Republic of Korea. Electronic address: kyslee@khu.ac.kr.
Yong Sup
YS
Lee
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D011485:Protein Binding; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012603:Scopoletin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship
C000591906:7-hydroxy-6-(3-(pyrrolidin-1-yl)propoxy)-2H-chromen-2-one; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D011759:Pyrrolidines; C030123:coumarin; D000110:Acetylcholinesterase; D012603:Scopoletin; C032519:pyrrolidine
Acetylcholinesterase inhibitor; Alzheimer’s disease; Coumarin; Galantamine; Memory; Scopoletin