Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia, and Institut de Biomedicina (IBUB), Universitat de Barcelona, Av. Diagonal 643, E-08028 Barcelona, Spain.
Chem Biol Interact. 2010 Sep 6;187(1-3):411-5. doi: 10.1016/j.cbi.2010.02.013. Epub 2010 Feb 16.
Two novel families of dual binding site acetylcholinesterase (AChE) inhibitors have been developed, consisting of a tacrine or 6-chlorotacrine unit as the active site interacting moiety, either the 5,6-dimethoxy-2-[(4-piperidinyl)methyl]-1-indanone fragment of donepezil (or the indane derivative thereof) or a 5-phenylpyrano[3,2-c]quinoline system, reminiscent to the tryciclic core of propidium, as the peripheral site interacting unit, and a linker of suitable length as to allow the simultaneous binding at both sites. These hybrid compounds are all potent and selective inhibitors of human AChE, and more interestingly, are able to interfere in vitro both formation and aggregation of the beta-amyloid peptide, the latter effects endowing these compounds with the potential to modify Alzheimer's disease progression.
已经开发出两种新型双结合位点乙酰胆碱酯酶 (AChE) 抑制剂家族，它们由他克林或 6-氯他克林单元作为活性位点相互作用部分，由多奈哌齐（或其茚满衍生物）的 5,6-二甲氧基-2-[(4-哌啶基)甲基]-1-茚酮片段或 5-苯基吡喃并[3,2-c]喹啉系统组成，类似于丙啶的三环核心，作为外围位点相互作用单元，以及适当长度的连接子，以允许同时结合两个位点。这些杂合化合物都是人类 AChE 的有效且选择性抑制剂，更有趣的是，它们能够在体外干扰β-淀粉样肽的形成和聚集，后者的作用使这些化合物具有改变阿尔茨海默病进展的潜力。
