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新型溴酚化合物的合成及其对碳酸酐酶和乙酰胆碱酯酶抑制作用的研究。

Synthesis of Novel Bromophenol with Diaryl Methanes-Determination of Their Inhibition Effects on Carbonic Anhydrase and Acetylcholinesterase.

机构信息

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum 25240, Turkey.

Department of Pharmacy Services, Gole Nihat Delibalta Vocational High School, Ardahan University, Ardahan 75000, Turkey.

出版信息

Molecules. 2022 Nov 1;27(21):7426. doi: 10.3390/molecules27217426.

Abstract

In this work, nine new bromophenol derivatives were designed and synthesized. The alkylation reactions of (2-bromo-4,5-dimethoxyphenyl)methanol () with substituted benzenes - produced new diaryl methanes -. Targeted bromophenol derivatives - were synthesized via the O-Me demethylation of diaryl methanes with BBr3. Moreover, the synthesized bromophenol compounds were tested with some metabolic enzymes such as acetylcholinesterase (AChE), carbonic anhydrase I (CA I), and II (CA II) isoenzymes. The novel synthesized bromophenol compounds showed Ki values that ranged from 2.53 ± 0.25 to 25.67 ± 4.58 nM against hCA I, from 1.63 ± 0.11 to 15.05 ± 1.07 nM against hCA II, and from 6.54 ± 1.03 to 24.86 ± 5.30 nM against AChE. The studied compounds in this work exhibited effective hCA isoenzyme and AChE enzyme inhibition effects. The results show that they can be used for the treatment of glaucoma, epilepsy, Parkinson's as well as Alzheimer's disease (AD) after some imperative pharmacological studies that would reveal their drug potential.

摘要

在这项工作中,设计并合成了九个新的溴酚衍生物。(2-溴-4,5-二甲氧基苯基)甲醇()与取代苯的烷基化反应-产生了新的二芳基甲烷。通过 BBr3 对二芳基甲烷进行 O-Me 脱甲基化,合成了目标溴酚衍生物。此外,还对合成的溴酚化合物进行了一些代谢酶(如乙酰胆碱酯酶(AChE)、碳酸酐酶 I(CA I)和 II(CA II)同工酶)的测试。新型合成的溴酚化合物对 hCA I 的 Ki 值范围为 2.53 ± 0.25 至 25.67 ± 4.58 nM,对 hCA II 的 Ki 值范围为 1.63 ± 0.11 至 15.05 ± 1.07 nM,对 AChE 的 Ki 值范围为 6.54 ± 1.03 至 24.86 ± 5.30 nM。本工作研究的化合物对 hCA 同工酶和 AChE 酶具有有效的抑制作用。结果表明,经过一些必要的药理学研究,它们可用于治疗青光眼、癫痫、帕金森病以及阿尔茨海默病(AD)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6364/9655968/8600499603e0/molecules-27-07426-g001.jpg

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