新型苯磺酰胺对碳酸酐酶和胆碱酯酶的硅学和体外抑制能力

IF 1.4 4区 化学 Q4 CHEMISTRY, INORGANIC & NUCLEAR
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引用次数: 0

摘要

具有苯磺酰胺结构的化合物被广泛应用于各个领域。据文献报道,许多属于这一类的化合物具有各种药理特性,如抗菌、抗真菌、抗病毒、抗癌、抗炎、抗青光眼和抗胆碱能作用。碳酸酐酶(CA)在 pH 值调节和长期突触转换中起着关键作用,因此被认为与智力迟钝、阿尔茨海默病(AD)和唐氏综合症等疾病有关。有研究报告称,在 AD 中,hCA-I 和 hCA-II 同工酶的水平会升高。阿兹海默病是一种复杂的多因素疾病,因此治疗可能不仅要针对胆碱能系统,还要针对其他系统。根据这些特点,研究人员从 1,2,3-三甲氧基-5-甲基苯合成了一系列新型取代苯磺酰胺。磺酰氯 9 是由 1,2,3-三甲氧基-5-甲基苯和过量的氯磺酸反应合成的。得到的磺酰氯与 NH3 和 N-烷基胺、苯胺和苯乙胺反应,得到取代苯磺酰胺衍生物 10-16。对合成化合物的碳酸酐酶(hCA I-II)、乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)抑制特性进行了评估。一些取代苯磺酰胺衍生物 10-16 对 hCA 同工酶具有抑制作用。对 hCA I 酶测定的 Ki 值范围为 102.01-147.19 µM。苯磺酰胺衍生物 10-16 对 AChE 和 BChE 具有抑制作用。AChE 和 BChE 酶的 Ki 值分别为 28.76-308.08 µM 和 42.80-445.60 µM。经测定,磺酰胺类化合物 15-16 对 hCA I 具有选择性抑制作用,其中 10 对 AChE 的选择性是 BChE 的 11 倍。此外,研究人员还对合成化合物的硅学 SAR 和 ADME 特性进行了研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In silico and in vitro inhibition abilities of novel benzene sulfonamides on carbonic anhydrase and choline esterases

Compounds that possess a benzene sulfonamide structure are utilized in a wide range of fields. It is reported in the literature that many compounds belonging to this class of compounds exhibit various pharmacological properties such as antibacterial, antifungal, antiviral, anticancer, inflammatory, antiglaucoma, and anticholinergic effects. Carbonic anhydrase (CA) enzymes play a critical role in pH regulation, long-term synaptic turnover and are therefore thought to be associated with such diseases as mental retardation, Alzheimer’s disease (AD) and Down syndrome. Studies have reported that there is an increase in the levels of hCA-I and hCA-II isoenzymes in AD. AD is a complex, multifactorial disorder, so therapy should probably address not only the cholinergic system but also additional systems. Based on these features, a series of novel substituted benzene sulfonamides were synthesized from 1,2,3-trimethoxy-5-methylbenzene. Sulfonyl chloride 9 was synthesized from the reaction of 1,2,3-trimethoxy-5-methylbenzene and excess chlorosulfonic acid. The reaction of the obtained sulfonyl chloride with NH3 and N-alkyl amines, aniline, and phenethylamine gave substituted benzene sulfonamide derivatives 1016. The synthesized compounds were evaluated for their carbonic anhydrase (hCA I-II), acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE) inhibitory properties. Some of the substituted benzene sulfonamide derivatives 1016 showed inhibitory effect on hCA isoenzymes. The Ki values determined for the hCA I enzyme are in the range of 102.01–147.19 µM. Benzene sulfonamide derivatives 1016 showed an inhibitory effect on AChE and BChE. The Ki values determined for AChE and BChE enzymes are in the range of 28.76–308.08 µM and 42.80–445.60 µM, respectively. It was determined that sulfonamides 1516 were selective inhibitors for the hCA I and 10 showed 11-fold more selectivity on AChE than BChE. In addition, the in-silico SAR and ADME properties of the synthesized compounds were also investigated.

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来源期刊
CiteScore
2.60
自引率
7.70%
发文量
103
审稿时长
2.1 months
期刊介绍: Phosphorus, Sulfur, and Silicon and the Related Elements is a monthly publication intended to disseminate current trends and novel methods to those working in the broad and interdisciplinary field of heteroatom chemistry.
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