3-取代噻唑鎓衍生物--阿拉吉铵的新类似物--的定向设计、筛选和抗糖化活性

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Olga N. Zhukovskaya, Alexandra A. Kolodina, Roman Litvinov, Umida Ibragimova, Nikita Valuisky, Svetlana Sorokina, Xenia Zhukova, Diana Yu. Pobedinskaya, Alexander Borisov, Denis A. Babkov, Alexander A. Spasov
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引用次数: 0

摘要

通过初步的 ab initio 计算,我们合成了新型取代的噻唑盐和 Alagebrium 类似物,并利用三种不同的检测方法:抑制荧光 AGEs 的形成、抗交联和降解,在体外进一步探讨了它们作为糖化反应抑制剂的潜力。尽管试验具有单向性,但在化合物的干扰机制和活性表现方面却发现了明显的差异。通过收集的数据,可以对所研究的抗糖化剂在每种测定中最重要的分子片段形成假设,从而指导未来的设计工作。其中还讨论了潜在的作用机制。化合物 4-甲基-3-[2-(4-甲基联苯-4-基)-2-氧代乙基]噻唑溴化物在所有三种试验中都显示出较高的活性,从而使其成为一种先导化合物。使用 LDH 和 MTT 检测法评估了这些化合物的细胞毒性特性。然而,先导化合物显示出细胞毒性,这表明需要进行更多研究,以在保持活性的同时降低毒性。目标噻唑盐是通过相应噻唑和苯酰溴之间的 N-烷基化反应合成的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Directed Design, Screening and Antiglycation Activity for 3-Substituted Thiazolium Derivatives, New Analogs of Alagebrium

Preliminary ab initio calculations led to the synthesis of novel substituted thiazolium salts, analogs of Alagebrium, which were further explored in vitro for their potential as inhibitors of the glycation reaction utilizing three distinct assays: inhibition of fluorescent AGEs formation, anticrosslinking, and deglycation. Despite the unidirectionality of the assays, distinct differences were observed in the mechanisms of interference and activity manifestation by the compounds. The gathered data permitted the formation of hypotheses about the molecular fragments of the studied antiglycators that are of utmost significance in each assay, thereby guiding future design endeavors. Potential mechanisms of actions are discussed therein. The compound 4-meth-yl-3-[2-(4-methylbiphenyl-4-yl)-2-oxoethyl] thiazolium bromide displayed high activity across all three assays, establishing it as a lead compound. The cytotoxicological properties of the compounds were evaluated using LDH and MTT assays. However, the lead compound exhibited cytotoxicity, indicating the need for additional investigations aimed at decreasing toxicity while maintaining activity. The targeted thiazolium salts were synthesized through an N-alkylation reaction between the corresponding thiazoles and phenacyl bromides.

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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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