Suppr超能文献

基于二环己胺胍的类似物:作为有前景的抗菌和抗糖化先导物的绿色化学合成、生物学研究及分子对接研究

Guanidine dicycloamine-based analogs: green chemistry synthesis, biological investigation, and molecular docking studies as promising antibacterial and antiglycation leads.

作者信息

El-Remaily Mahmoud Abd El Aleem A A, Aboelez Moustafa O, Ezelarab Hend A A, Selim Heba Mohammed Refat M, Taha Enas A, Mohamed Shaaban K, Soliman Ahmed M, Abdallah Mohamed S, Fawy Mariam A, Hassany Mohamed A, Ahmed Nessar, Alsaggaf Azhaar T, El Hamd Mohamed A, Kamel Moumen S

机构信息

Department of Chemistry, Faculty of Science, Sohag University, Sohag, 82524, Egypt.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag, 82524, Egypt.

出版信息

Mol Divers. 2024 Dec;28(6):4277-4299. doi: 10.1007/s11030-024-10816-w. Epub 2024 Feb 7.

Abstract

Dicyandiamide (DCD) reacted with amino acids 1a-f to produce biguanides 2 and 4 and guanidine pyrazolones 3, 5, 6, 7, and 8, according to the reaction. DCD exhibited the following reactions: imidodicarbonimidicdiamide 9, diazocan-2-ylguanidine 10, methyl biguanidylthion 11, N-carbamothioylimidodicarbonimidicdiamide 12, 2-guanidinebenzoimidazole 13a, 2-guanidinylbenzoxazole 13b, and 2-guanidinylbenzothiazol 13c. These reactions were triggered by 6-amino caproic acid, thioacetamide, thiourea, o-aminophenol, o-aminothiophenol, and anthranilic acid, respectively. Compound 2 had the least antimicrobial activity, while compound 13c demonstrated the most antibacterial impact against all bacterial strains. Furthermore, in terms of antiglycation efficacy (AGEs), 12, 11, and 7 were the most effective AGE cross-linking inhibitors. Eight and ten, which showed a considerable inhibition on cross-linking AGEs, come next. Compounds 4 and 6 on the other hand have shown the least suppression of AGE production. The most promising antiglycation scaffolds 8, 11, and 12 in the Human serum albumin (HAS) active site were shown to be able to adopt crucial binding interactions with important amino acids based on the results of in silico molecular docking. The most promising antiglycation compounds 8, 11, and 12 were also shown to have better hydrophilicity, acceptable lipophilicity, gastrointestinal tract absorption (GIT), and blood-brain barrier penetration qualities when their physicochemical properties were examined using the egg-boiled method.

摘要

根据反应,双氰胺(DCD)与氨基酸1a - f反应生成双胍2和4以及胍基吡唑啉酮3、5、6、7和8。DCD呈现出以下反应:亚氨基二碳酰二胺9、重氮环庚 - 2 - 基胍10、甲基双胍基硫酮11、N - 氨基甲酰硫基亚氨基二碳酰二胺12、2 - 胍基苯并咪唑13a、2 - 胍基苯并恶唑13b和2 - 胍基苯并噻唑13c。这些反应分别由6 - 氨基己酸、硫代乙酰胺、硫脲、邻氨基酚、邻氨基苯硫酚和邻氨基苯甲酸引发。化合物2的抗菌活性最低,而化合物13c对所有细菌菌株的抗菌作用最强。此外,就抗糖化功效(晚期糖基化终末产物,AGEs)而言,12、11和7是最有效的AGE交联抑制剂。其次是对AGE交联有显著抑制作用的8和10。另一方面,化合物4和6对AGE生成的抑制作用最小。基于计算机模拟分子对接结果,在人血清白蛋白(HAS)活性位点中最有前景的抗糖化支架8、11和12能够与重要氨基酸形成关键的结合相互作用。当使用煮鸡蛋法检测其理化性质时,最有前景的抗糖化化合物8、11和12还表现出更好的亲水性、可接受的脂溶性、胃肠道吸收(GIT)和血脑屏障穿透特性。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验