石杉碱甲-他克林杂合物作为靶向人类胆碱酯酶中峡识别位点的强效抑制剂的发现。
Discovery of huperzine A-tacrine hybrids as potent inhibitors of human cholinesterases targeting their midgorge recognition sites.
作者信息
Gemma Sandra, Gabellieri Emanuele, Huleatt Paul, Fattorusso Caterina, Borriello Marianna, Catalanotti Bruno, Butini Stefania, De Angelis Meri, Novellino Ettore, Nacci Vito, Belinskaya Tatyana, Saxena Ashima, Campiani Giuseppe
机构信息
Dipartimento Farmaco Chimico Tecnologico, Via Aldo Moro, Universita' di Siena, 53100 Siena, Italy.
出版信息
J Med Chem. 2006 Jun 1;49(11):3421-5. doi: 10.1021/jm060257t.
We describe herein the development of novel huperzine A-tacrine hybrids characterized by 3-methylbicyclo[3.3.1]non-3-ene scaffolds. These compounds were specifically designed to establish tight interactions, through different binding modes, with the midgorge recognition sites of human acetylcholinesterase (hAChE: Y72, D74) and human butyrylcholinesterase (hBuChE: N68, D70) and their catalytic or peripheral sites. Compounds 5a-c show a markedly improved biological profile relative to tacrine and huperzine A.
我们在此描述了以3-甲基双环[3.3.1]壬-3-烯骨架为特征的新型石杉碱甲-他克林杂合物的开发。这些化合物经过专门设计，通过不同的结合模式与人类乙酰胆碱酯酶（hAChE：Y72、D74）和人类丁酰胆碱酯酶（hBuChE：N68、D70）的中间峡谷识别位点及其催化或外周位点建立紧密相互作用。与他克林和石杉碱甲相比，化合物5a-c显示出明显改善的生物学特性。
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