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

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 est...

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Main Authors: M. D. Korotkin, S. M. Filatova, Z. G. Denieva, U. A. Budanova, Y. L. Sebyakin
Format: Article
Language:Russian
Published: MIREA - Russian Technological University 2022-04-01
Series:Тонкие химические технологии
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Online Access:https://www.finechem-mirea.ru/jour/article/view/1799
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author M. D. Korotkin
S. M. Filatova
Z. G. Denieva
U. A. Budanova
Y. L. Sebyakin
author_facet M. D. Korotkin
S. M. Filatova
Z. G. Denieva
U. A. Budanova
Y. L. Sebyakin
author_sort M. D. Korotkin
collection DOAJ
description 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.
format Article
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institution Kabale University
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publisher MIREA - Russian Technological University
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series Тонкие химические технологии
spelling doaj-art-421f365fa2334912a5cce1ec618cf8342025-08-20T03:56:32ZrusMIREA - Russian Technological UniversityТонкие химические технологии2410-65932686-75752022-04-01171506410.32362/2410-6593-2022-17-1-50-641668Synthesis of diethanolamine-based amino acid derivatives with symmetric and asymmetric radicals in their hydrophobic domain and potential antimicrobial activityM. D. Korotkin0S. M. Filatova1Z. G. Denieva2U. A. Budanova3Y. L. Sebyakin4MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of SciencesMIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)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.https://www.finechem-mirea.ru/jour/article/view/1799antimicrobial peptidesantibacterial agentsresistancehydrophilic-lipophilic balanceamphiphilesamino acidsdiethanolamine esters
spellingShingle M. D. Korotkin
S. M. Filatova
Z. G. Denieva
U. A. Budanova
Y. L. Sebyakin
Synthesis of diethanolamine-based amino acid derivatives with symmetric and asymmetric radicals in their hydrophobic domain and potential antimicrobial activity
Тонкие химические технологии
antimicrobial peptides
antibacterial agents
resistance
hydrophilic-lipophilic balance
amphiphiles
amino acids
diethanolamine esters
title Synthesis of diethanolamine-based amino acid derivatives with symmetric and asymmetric radicals in their hydrophobic domain and potential antimicrobial activity
title_full Synthesis of diethanolamine-based amino acid derivatives with symmetric and asymmetric radicals in their hydrophobic domain and potential antimicrobial activity
title_fullStr Synthesis of diethanolamine-based amino acid derivatives with symmetric and asymmetric radicals in their hydrophobic domain and potential antimicrobial activity
title_full_unstemmed Synthesis of diethanolamine-based amino acid derivatives with symmetric and asymmetric radicals in their hydrophobic domain and potential antimicrobial activity
title_short Synthesis of diethanolamine-based amino acid derivatives with symmetric and asymmetric radicals in their hydrophobic domain and potential antimicrobial activity
title_sort synthesis of diethanolamine based amino acid derivatives with symmetric and asymmetric radicals in their hydrophobic domain and potential antimicrobial activity
topic antimicrobial peptides
antibacterial agents
resistance
hydrophilic-lipophilic balance
amphiphiles
amino acids
diethanolamine esters
url https://www.finechem-mirea.ru/jour/article/view/1799
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AT zgdenieva synthesisofdiethanolaminebasedaminoacidderivativeswithsymmetricandasymmetricradicalsintheirhydrophobicdomainandpotentialantimicrobialactivity
AT uabudanova synthesisofdiethanolaminebasedaminoacidderivativeswithsymmetricandasymmetricradicalsintheirhydrophobicdomainandpotentialantimicrobialactivity
AT ylsebyakin synthesisofdiethanolaminebasedaminoacidderivativeswithsymmetricandasymmetricradicalsintheirhydrophobicdomainandpotentialantimicrobialactivity