Synthesis of diethanolamine-based amino acid derivatives with symmetric and asymmetric radicals in their hydrophobic domain and potential antimicrobial activity

M. D. Korotkin, S. M. Filatova, Z. Denieva, U. A. Budanova, Y. Sebyakin
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引用次数: 2

Abstract

Objectives. Resistance to antibiotics and other antimicrobial drugs is an acute problem in the world today. Therefore, the chemical and pharmaceutical industries are still in search of new antibacterial agents that can overcome the resistance of pathogenic bacterial strains. To date, it has been established that molecules with antimicrobial activity must have an amphiphilic nature, a small size, one or more positive charges, and the required degree of hydrophobicity, that is, a significant hydrophilic–lipophilic balance (HLB) value. Some examples of such structures are antimicrobial peptides or peptidomimetics. This study aimed to develop a universal scheme for synthesizing several amino acid derivatives based on diethanolamine diesters with symmetric and asymmetric radicals in a hydrophobic block and potential antibacterial activity.Methods. The progression of chemical reactions was analyzed using thin-layer chromatography (TLC) on Sorbfil plates. The obtained compounds were isolated and purified using preparative TLC on Kieselgel (Merck) 60 F254 plates and column chromatography on Merck silica gel 0.040–0.063 mm. The TLC method was used to detect substances using a 3% ninhydrin solution, followed by heating to 70 °C. The structures of the obtained compounds were confirmed by hydrogen-1 nuclear magnetic resonance (1H NMR) spectroscopy on a Bruker WM-300 pulse NMR spectrometer, with hexamethyldisiloxane serving as the internal standard.Results. The HLB values of the diethanolamine derivatives were calculated, and samples were selected for subsequent synthesis. A scheme was developed for preparing amino acid derivatives based on diethanolamine diesters with symmetric and asymmetric radicals in the hydrophobic domain, and five new compounds were synthesized. The hydrophilic blocks of these compounds included residues of amino acids such as glycine, β-alanine, L-ornithine, and L-lysine.Conclusions. The potential antimicrobial activity of the synthesized peptidomimetics was assessed by their HLB values using the ACD/Labs Log P program. New amphiphiles were synthesized using amino acids and diethanolamine, and their structures were confirmed by 1H NMR spectroscopy data. The synthesized compounds were prepared for antibacterial activity analysis.
基于二乙醇胺的氨基酸衍生物的对称和不对称疏水自由基的合成及其潜在的抗菌活性
目标。对抗生素和其他抗微生物药物的耐药性是当今世界的一个严重问题。因此,化学和制药工业仍在寻找新的抗菌剂,可以克服病原菌菌株的耐药性。迄今为止,已经确定具有抗菌活性的分子必须具有两亲性,体积小,一个或多个正电荷,以及所需的疏水性程度,即显著的亲水-亲脂平衡(HLB)值。这种结构的一些例子是抗菌肽或拟肽。本研究旨在建立一种以二乙醇胺二酯为基础,具有对称和不对称疏水基团的氨基酸衍生物的合成方法,并研究其潜在的抗菌活性。在Sorbfil板上用薄层色谱法分析了化学反应的过程。在Kieselgel (Merck) 60 F254板上进行制备层析,在Merck硅胶0.040-0.063 mm上进行柱层析。采用薄层色谱法,采用3%茚三醇溶液,加热至70℃。以六甲基二硅氧烷为内标,在Bruker WM-300脉冲核磁共振波谱仪上用氢-1核磁共振(1H NMR)谱法对所得化合物的结构进行了确证。计算二乙醇胺衍生物的HLB值,并选择样品进行后续合成。提出了一种以二乙醇胺二酯为基础,在疏水区域具有对称和不对称自由基的氨基酸衍生物的制备方案,并合成了5个新化合物。这些化合物的亲水性块包括氨基酸残基,如甘氨酸、β-丙氨酸、l -鸟氨酸和l -赖氨酸。利用ACD/Labs Log P程序通过HLB值评估合成的拟肽物的潜在抗菌活性。以氨基酸和二乙醇胺为原料合成了新的两亲体,并用1H NMR数据对其结构进行了验证。对合成的化合物进行抗菌活性分析。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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