Discovery of huperzine A-tacrine hybrids as potent inhibitors of human cholinesterases targeting their midgorge recognition sites.

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Gemma S, Gabellieri E, Huleatt P, Fattorusso C, Borriello M, Catalanotti B, Butini S, De Angelis M, Novellino E, Nacci V, Belinskaya T, Saxena A, Campiani G

Discovery of huperzine A-tacrine hybrids as potent inhibitors of human cholinesterases targeting their midgorge recognition sites.

J Med Chem. 2006 Jun 1;49(11):3421-5.

PubMed ID
16722663 [ View in PubMed
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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
3-Chloro-9-Ethyl-6,7,8,9,10,11-Hexahydro-7,11-Methanocycloocta[B]Quinolin-12-AmineAcetylcholinesteraseKi (nM)0.026825Details
Huperzine AAcetylcholinesteraseKi (nM)47825Details
TacrineAcetylcholinesteraseKi (nM)137825Details