Boulebd Houssem, Ismaili Lhassane, Martin Helene, Bonet Alexandre, Chioua Mourad, Marco Contelles José, Belfaitah Ali
Laboratoire des Produits Naturels d'Origine Végétale et de Synthèse Organique. Faculté des Sciences Exactes, Campus de Chaabat Ersas, Université des frères Mentouri-Constantine. Constantine 25000, Algeria.
Laboratoire de Chimie Organique et Thérapeutique, Neurosciences intégratives et cliniques EA 481, UFR SMP, 19 rue Ambroise Paré, Université Bourgogne Franche-Comté, F-25000 Besançon Cedex, France.
Future Med Chem. 2017 May;9(8):723-729. doi: 10.4155/fmc-2017-0019. Epub 2017 May 9.
Due to the multifactorial nature of Alzheimer's disease, there is an urgent search for new more efficient, multitarget-directed drugs.
This paper describes the synthesis, antioxidant and in vitro biological evaluation of ten (benz)imidazopyridino tacrines (7-16), showing less toxicity than tacrine at high doses, and potent cholinesterase inhibitory capacity, in the low micromolar range. Among them, compound 10 is a nonhepatotoxic tacrine at 1000 mM, showing moderate, but totally selective electric eel acetylcholinesterase inhibition, whereas molecule 16 is twofold less toxic than tacrine at 1000 μM, showing moderate and almost equipotent inhibition for electric eel acetylcholinesterase and equine butyrylcholinesterase.
(Benz)imidazopyridino tacrines (7-16) have been identified as a new and promising type of tacrines for the potential treatment of Alzheimer's disease.
由于阿尔茨海默病的多因素性质，迫切需要寻找新的、更高效的多靶点导向药物。
本文描述了十种（苯并）咪唑并吡啶基他克林（7 - 16）的合成、抗氧化及体外生物学评价，这些化合物在高剂量时毒性低于他克林，且在低微摩尔范围内具有强大的胆碱酯酶抑制能力。其中，化合物10在1000 mM时为非肝毒性他克林，对电鳗乙酰胆碱酯酶表现出中等但完全选择性的抑制作用；而分子16在1000 μM时毒性比他克林低两倍，对电鳗乙酰胆碱酯酶和马源丁酰胆碱酯酶表现出中等且几乎等效的抑制作用。
（苯并）咪唑并吡啶基他克林（7 - 16）已被确定为一种新型且有前景的他克林类型，有望用于治疗阿尔茨海默病。
Zotero 插件