Lee Young Hun, Shin Min Cheol, Yun Yong Don, Shin Seo Young, Kim Jong Min, Seo Jeong Moo, Kim Nam-Jung, Ryu Jong Hoon, Lee Yong Sup
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, 26 Kyungheedae-ro, Seoul 130-701, Republic of Korea; Medicinal Chemistry Laboratory, Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 130-701, Republic of Korea.
Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 130-701, Republic of Korea.
Bioorg Med Chem. 2015 Jan 1;23(1):231-40. doi: 10.1016/j.bmc.2014.11.004. Epub 2014 Nov 13.
Alzheimer's disease (AD), a progressive and neurodegenerative disorder of the brain, is the most common cause of dementia among elderly people. To date, the successful therapeutic strategy to treat AD is maintaining the levels of acetylcholine by inhibiting acetylcholinesterase (AChE). In the present study, aurone derivatives were designed and synthesized as AChE inhibitors based on the lead structure of sulfuretin. Of those synthesized, compound 10d showed ca. 1700-fold and 6-fold higher AChE inhibitory activity than sulfuretin and galantamine, respectively. This compound also ameliorated scopolamine-induced memory deficit in mice when administered orally at the dose of 1 and 2mg/kg.
阿尔茨海默病（AD）是一种进行性神经退行性脑部疾病，是老年人痴呆最常见的病因。迄今为止，治疗AD的成功治疗策略是通过抑制乙酰胆碱酯酶（AChE）来维持乙酰胆碱水平。在本研究中，基于硫黄菊素的先导结构设计并合成了橙酮衍生物作为AChE抑制剂。在合成的化合物中，化合物10d对AChE的抑制活性分别比硫黄菊素和加兰他敏高约1700倍和6倍。当以1和2mg/kg的剂量口服给药时，该化合物还改善了东莨菪碱诱导的小鼠记忆缺陷。
