vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"vestich-288Research ArticleОРГАНИЧЕСКАЯ ХИМИЯORGANIC CHEMISTRYСИНТЕЗ ГИДРОФИЛЬНЫХ ПРОИЗВОДНЫХ 11,11-D2-ЛИНОЛЕВОЙ КИСЛОТЫSYNTHESIS OF HYDROPHILIC DERIVATIVES OF 11,11-D2-LINOLEIC ACIDФомичМ. А.FomichM. A.

науч. сотрудник

ул. Сурганова, 13, 220072

Researcher

13, Surganov Str., 220072

mfomich@gmail.comШаркоО. Л.SharkoO. L.

канд. хим. наук, ст. на- уч. сотрудник

ул. Сурганова, 13, 220072

Ph. D. (Chemistry), Senior Researcher

13, Surganov Str., 220072

sharko@ifoch.bas-net.byШманайВ. В.ShmanaiV. V.

канд. хим. наук, зав. лаб. химии биоконъюгатов

ул. Сурганова, 13, 220072

Ph. D. (Chemistry), Head of the Laboratory of Bioconjugate Chemistry

13, Surganov Str., 220072

shmanai@ifoch.bas-net.byИнститут физико-органической химии НАН Беларуси, МинскInstitute of Physical Organic Chemistry of the National Academy of Sciences of Belarus, Minsk201714122017044854Copyright © Фомич М.А., Шарко О.Л., Шманай В.В., 20172017Фомич М.А., Шарко О.Л., Шманай В.В.Fomich M.A., Sharko O.L., Shmanai V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/288

Ранее показано, что 11,11-D2-линолевая кислота эффективно подавляет процессы липидного окисления in vitro и в клеточных культурах за счет наличия в ее структуре «усиленных» С-D-связей в бис-аллильных положениях, наиболее чувствительных к действию радикалов. Как следствие, это соединение является перспективным кандидатом в терапии митохондриальных и глазных заболеваний. В данной работе решается задача синтеза гидрофильных производных 11,11-D2-линолевой кислоты, которые могут служить ее пролекарственными формами с увеличенной растворимостью в воде и биологических средах и улучшенными фармакологическими параметрами. В качестве модифицирующих реагентов мы выбрали биологически совместимые природные соединения, преимущественно аминокислоты, присоединяемые к 11,11-D2-линолевой кислоте амидной или сложноэфирной связью. Среди полученных соединений присутствуют катионные, анионные и незаряженные производные, которые в дальнейшем планируется испытать на их способность проникать к сетчатке глаза. 

Previously it was shown that 11,11-D2-linoleic acid effectively quenches the processes of lipid peroxidation in vitro and in cell cultures due to the presence of reinforced C-D bonds in bis-allylic positions, which are most vulnerable to the radicals. Therefore, this compound serves as a promising candidate to treat mitochondrial and eye diseases. The present work deals with the synthesis of the hydrophilic derivatives of 11,11-D2-linoleic acid as prodrug forms with increased solubility in water and biological media and improved pharmacological properties. As modifying reagents, we chose biologically compatible natural compounds, mainly aminoacids, which were attached to 11,11-D2-linoleic acid via amide or ester bond. Among the synthesized compounds there are cationic, anionic and neutral derivatives, and their permeability in eyes will be further tested. 

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The authors declare that there are no conflicts of interest present.