One-Pot Syntheses and Enzyme Inhibition Studies of New C-28 Ester Derivatives of Betulinic Acid

IF 0.7 4区化学 Q4 CHEMISTRY, ORGANIC

Letters in Organic Chemistry Pub Date : 2024-08-12 DOI:10.2174/0115701786324362240726102810

Muhammad Shaiq Ali, Sumera Shezadi, Azra Akbar, Humaira Zafar, Muhammad Imran Malik, Mahreen Lateef

{"title":"One-Pot Syntheses and Enzyme Inhibition Studies of New C-28 Ester Derivatives of Betulinic Acid","authors":"Muhammad Shaiq Ali, Sumera Shezadi, Azra Akbar, Humaira Zafar, Muhammad Imran Malik, Mahreen Lateef","doi":"10.2174/0115701786324362240726102810","DOIUrl":null,"url":null,"abstract":": Betulinic acid and its various synthetic derivatives have been reported to possess diverse biological activities and some of these may serve as useful therapeutic agents for a variety of human disorders. In this perspective, we have now developed convenient one-pot syntheses of new C-28 esters (2-7) of betulinic acid by esterification of the carboxylic moiety of betulinic acid (1) with various alkylating agents. All the target compounds were subjected to enzyme inhibition studies to ascertain their possible therapeutic utility. Compound 5 showed very potent lipoxygenase inhibitory activity with an IC50 value of 13.2 μM, being much lower than the IC50 value of 22.4 μM of baicalein, which was used as the standard. Butulinic acid itself and compound 6 also showed significant inhibitory potential (IC50: 32.4 and 25.1 μM) against the same enzyme. The activities of both compounds 5 and 6 have been justified by intensive docking studies. Compounds 2 and 3 exhibited substantial inhibition (IC50: 18.4 and 21.5 μM) against the enzyme butrylcholinesterase, compared to serine used as the standard (IC50: 7.8 μM).","PeriodicalId":18116,"journal":{"name":"Letters in Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":0.7000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Letters in Organic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.2174/0115701786324362240726102810","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}

引用次数: 0

Abstract

: Betulinic acid and its various synthetic derivatives have been reported to possess diverse biological activities and some of these may serve as useful therapeutic agents for a variety of human disorders. In this perspective, we have now developed convenient one-pot syntheses of new C-28 esters (2-7) of betulinic acid by esterification of the carboxylic moiety of betulinic acid (1) with various alkylating agents. All the target compounds were subjected to enzyme inhibition studies to ascertain their possible therapeutic utility. Compound 5 showed very potent lipoxygenase inhibitory activity with an IC50 value of 13.2 μM, being much lower than the IC50 value of 22.4 μM of baicalein, which was used as the standard. Butulinic acid itself and compound 6 also showed significant inhibitory potential (IC50: 32.4 and 25.1 μM) against the same enzyme. The activities of both compounds 5 and 6 have been justified by intensive docking studies. Compounds 2 and 3 exhibited substantial inhibition (IC50: 18.4 and 21.5 μM) against the enzyme butrylcholinesterase, compared to serine used as the standard (IC50: 7.8 μM).

查看原文本刊更多论文

白桦脂酸 C-28 酯新衍生物的一锅合成和酶抑制研究

:据报道，白桦脂酸及其各种合成衍生物具有多种生物活性，其中一些可作为治疗各种人类疾病的有用药物。从这个角度出发，我们通过白桦脂酸（1）的羧基与各种烷化剂的酯化反应，开发出了方便的白桦脂酸 C-28 新酯（2-7）的一锅合成方法。对所有目标化合物都进行了酶抑制研究，以确定其可能的治疗作用。化合物 5 显示出非常强的脂氧合酶抑制活性，其 IC50 值为 13.2 μM，远低于作为标准的黄芩素的 IC50 值 22.4 μM。丁二酸本身和化合物 6 也对同一种酶表现出明显的抑制潜力（IC50：32.4 和 25.1 μM）。深入的对接研究证明了化合物 5 和 6 的活性。与作为标准物质的丝氨酸（IC50：7.8 μM）相比，化合物 2 和 3 对丁酰胆硷酯酶具有很强的抑制作用（IC50：18.4 和 21.5 μM）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Letters in Organic Chemistry 化学-有机化学

CiteScore

1.30

自引率

12.50%

发文量

135

审稿时长

7 months

期刊介绍： Aims & Scope Letters in Organic Chemistry publishes original letters (short articles), research articles, mini-reviews and thematic issues based on mini-reviews and short articles, in all areas of organic chemistry including synthesis, bioorganic, medicinal, natural products, organometallic, supramolecular, molecular recognition and physical organic chemistry. The emphasis is to publish quality papers rapidly by taking full advantage of latest technology for both submission and review of the manuscripts. The journal is an essential reading for all organic chemists belonging to both academia and industry.