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新型双结合位点胆碱酯酶抑制剂的设计与合成：基于对接的抑制研究

Design and Synthesis of New Dual Binding Site Cholinesterase Inhibitors: Inhibition Studies with Docking.

作者信息

Yar Muhammad, Bajda Marek, Mehmood Rana Atif, Sidra Lala Rukh, Ullah Nisar, Shahzadi Lubna, Ashraf Muhammad, Ismail Tayaba, Shahzad Sohail Anjum, Khan Zulfiqar Ali, Naqvi Syed Ali Raza, Mahmood Nasir

机构信息

Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore, 54000, Pakistan.

Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Pasteura 1, Poland and Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Cracow, Medyczna 9, Poland.

出版信息

Lett Drug Des Discov. 2014 Mar;11(3):331-338. doi: 10.2174/15701808113106660078.

DOI:10.2174/15701808113106660078
PMID:24719609
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3977535/
Abstract

Cholinesterases (ChEs) play a vital role in the regulation of cholinergic transmission. The inhibition of ChEs is considered to be involved in increasing acetylcholine level in the brain and thus has been implicated in the treatment of Alzheimer's disease. We have designed and synthesized a series of novel indole derivatives and screened them for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of the tested compounds exhibited inhibitory activity against AChE and BChE. Among them and showed the highest AChE inhibitory activity with IC 91.21±0.06 and 68.52±0.04 μM, respectively. However compound exhibited the highest inhibitory activity against BChE (IC 55.21±0.12 μM).

摘要

胆碱酯酶（ChEs）在胆碱能传递的调节中起着至关重要的作用。胆碱酯酶的抑制被认为与提高大脑中的乙酰胆碱水平有关，因此一直被用于阿尔茨海默病的治疗。我们设计并合成了一系列新型吲哚衍生物，并对它们抑制乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的活性进行了筛选。大多数测试化合物对AChE和BChE均表现出抑制活性。其中，[具体化合物1]和[具体化合物2]对AChE的抑制活性最高，IC50分别为91.21±0.06和68.52±0.04 μM。然而，化合物[具体化合物3]对BChE表现出最高的抑制活性（IC50为55.21±0.12 μM）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64a/3977535/6f57fe120ca2/LDDD-11-331_S1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64a/3977535/d99466b34023/LDDD-11-331_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64a/3977535/33882ba05c88/LDDD-11-331_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64a/3977535/eb6cadc0aa4d/LDDD-11-331_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64a/3977535/6f57fe120ca2/LDDD-11-331_S1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64a/3977535/d99466b34023/LDDD-11-331_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64a/3977535/33882ba05c88/LDDD-11-331_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64a/3977535/eb6cadc0aa4d/LDDD-11-331_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64a/3977535/6f57fe120ca2/LDDD-11-331_S1.jpg

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