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1,2,3,4,6-五取代-4-羟基环己烷的乙酰胆碱酯酶和碳酸酐酶抑制谱评估

Evaluation of acetylcholinesterase and carbonic anhydrase inhibition profiles of 1,2,3,4,6-pentasubstituted-4-hydroxy-cyclohexanes.

作者信息

Kocyigit Umit M, Taslimi Parham, Gezegen Hayreddin, Gulçin İlhami, Ceylan Mustafa

机构信息

Vocational School of Health Services, Cumhuriyet University, Sivas, Turkey.

Department of Chemistry, Faculty of Sciences, Ataturk University, Erzurum, Turkey.

出版信息

J Biochem Mol Toxicol. 2017 Sep;31(9). doi: 10.1002/jbt.21938. Epub 2017 Jun 14.

Abstract

Carbonic anhydrase (CA; EC 4.2.1.1) is used for remedial purposes for several years, as there is significant focus on expanding more new activators (CAAs) and high affinity inhibitors. Alzheimer's disease and other similar ailments such as dementia and vascular dementia with Lewy bodies reduce cholinergic activity in the important areas involved in cognition and memory. Prevalent drugs for the symptomatic therapy of dementia are significant in increasing the associated cholinergic deficiency by inhibiting acetylcholinesterase (AChE). These six-membered carbocycles showed nice inhibitory action against AChE and human carbonic anhydrase (hCA) II and I isoforms. The hCA I, II, and AChE were efficiently inhibited by these molecules, with K values in the range of 6.70-35.85 nM for hCA I, 18.77-60.84 nM for hCA II, and 0.74-4.60 for AChE, respectively.

摘要

碳酸酐酶(CA;EC 4.2.1.1)已用于治疗目的数年,因为人们非常关注开发更多新型激活剂(CAA)和高亲和力抑制剂。阿尔茨海默病以及其他类似疾病,如痴呆症和路易体血管性痴呆,会降低认知和记忆所涉及的重要区域的胆碱能活性。用于痴呆症症状治疗的常用药物通过抑制乙酰胆碱酯酶(AChE)来显著增加相关的胆碱能缺乏。这些六元碳环对AChE和人碳酸酐酶(hCA)II和I同工型表现出良好的抑制作用。这些分子有效抑制了hCA I、II和AChE,hCA I的K值范围为6.70 - 35.85 nM,hCA II为18.77 - 60.84 nM,AChE为0.74 - 4.60。

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