pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2023-12-4-1521pharmjournal-1652Research ArticleПОИСК И РАЗРАБОТКА НОВЫХ ЛЕКАРСТВЕННЫХ СРЕДСТВRESEARCH AND DEVELOPMENT OF NEW DRUG PRODUCTSЛекарственные перспективы ретиноидов (обзор)Medicinal Perspectives of Retinoids (Review)https://orcid.org/0000-0002-0027-4664КоваленкоЛ. В.KovalenkoL. V.

125047, г. Москва, Миусская площадь, д. 9

9, Miusskaya square, Moscow, 125047

https://orcid.org/0000-0003-4502-0745ПоливановаА. Г.PolivanovaA. G.

125047, г. Москва, Миусская площадь, д. 9

9, Miusskaya square, Moscow, 125047

polivanova.a.g@muctr.ruhttps://orcid.org/0009-0008-5177-2867ИльинА. П.IlyinA. P.

141401, Московская область, г. Химки, ул. Рабочая, д. 2А, стр. 1

2A/1, Rabochaya str., Khimki, Moscow region, 141401

https://orcid.org/0000-0002-0079-6710СоловьеваИ. Н.SolovievaI. N.

125047, г. Москва, Миусская площадь, д. 9

9, Miusskaya square, Moscow, 125047

https://orcid.org/0009-0009-3829-8109ГорбачеваЕ. И.GorbachevaE. I.

117997, г. Москва, ГСП-7, ул. Миклухо-Маклая, д. 16/10

16/10, Miklouho-Maklaya str., GSP-7, Moscow, 117997 

https://orcid.org/0000-0002-2892-4884ОщепковМ. С.OshchepkovM. S.

125047, г. Москва, Миусская площадь, д. 9

9, Miusskaya square, Moscow, 125047

Федеральное государственное бюджетное образовательное учреждение высшего образования «Российский химико-технологический университет имени Д. И. Менделеева» (РХТУ им. Д. И. Менделеева)РоссияD. Mendeleev University of Chemical Technology of Russia (D. Mendeleev University, MUCTR)Russian FederationОбщество с ограниченной ответственностью «АФС-технологии»РоссияLLC «AFS-technologies»Russian FederationФедеральное государственное бюджетное учреждение науки Институт биоорганической химии им. академиков М. М. Шемякина и Ю. А. Овчинникова Российской академии наук (ИБХ РАН)РоссияShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS (IBCh RAS)Russian Federation2023111120231245462Copyright © Коваленко Л.В., Поливанова А.Г., Ильин А.П., Соловьева И.Н., Горбачева Е.И., Ощепков М.С., 20232023Коваленко Л.В., Поливанова А.Г., Ильин А.П., Соловьева И.Н., Горбачева Е.И., Ощепков М.С.Kovalenko L.V., Polivanova A.G., Ilyin A.P., Solovieva I.N., Gorbacheva E.I., Oshchepkov M.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/1652Введение

Введение. Ретиноиды представляют собой группу эндогенных и синтетических веществ, регулирующих множество важных биологических процессов нормального развития. Синтез и изучение биологической активности новых ретиноидов являются перспективной областью химической биологии.

Текст

Текст. Геномные функции ретиноидов опосредованы их ядерными рецепторами RAR(α, β, γ) и RXR(α, β, γ), которые регулируют транскрипцию генов с привлечением корепрессоров и коактиваторов. Ретиноиды также обладают негеномными функциями, ацилируя белки и другие биомолекулы. Передовыми областями исследований биологической активности ретиноидов являются регенеративная медицина и биология стволовых клеток. Эндогенные и синтетические ретиноиды применяются для лечения кожных патологий и онкологических заболеваний. Есть данные о возможности использования их в терапии заболеваний легких. Разработка ретиноидов, обладающих высокой селективностью в отношении отдельных рецепторов и тканей, может открыть новые подходы к лечению и профилактике таких нейродегенеративных заболеваний, как болезнь Альцгеймера, болезнь Паркинсона и другие. Ретиноиды необходимы для функционирования иммунной системы и являются очень мощными иммуномодуляторами. Кроме того, ретиноиды обладают потенциалом для терапии различных пролиферативных заболеваний.

Заключение

Заключение. Многолетние исследования фармакологической активности ретиноевой кислоты и ее структурных аналогов направлены на изучение и установление точных механизмов их действия, а также степени их участия в патогенезе различных заболеваний. Получение синтетических ретиноидов преследует цель дизайна соединений с высокой избирательностью по отношению к определенным рецепторам, что позволило бы исключить мультитаргетное действие естественных регуляторных молекул и обусловленные этим побочные эффекты. Лишенные тератогенных и других побочных эффектов синтетические ретиноиды могут найти применение в качестве терапевтических средств для лечения дефектного метаболизма, различных злокачественных новообразований, а также заболеваний почек, легких и ЦНС. Кроме того, разработка пролекарств на основе ретиноидов с контролируемым высвобождением активных молекул также является перспективным направлением в этой области медицинской химии.

Introduction

Introduction. Retinoids are a group of endogenous and synthetic substances that regulate numerous important biological processes in normal development. The synthesis and study of the biological activity of new retinoids are a promising area of chemical biology.

Text

Text. The genomic functions of retinoids are mediated by their nuclear receptors RAR(α, β, γ) and RXR(α, β, γ), which regulate gene transcription by recruiting corepressors and coactivators. Retinoids also possess non-genomic functions by acylating proteins and other biomolecules. Regenerative medicine and stem cell biology are advanced areas of research in the biological activity of retinoids. Endogenous and synthetic retinoids are used for the treatment of skin pathologies and in oncology. There is evidence of their potential use in the therapy of lung diseases. The development of retinoids with high selectivity towards specific receptors and tissues may open new approaches to the treatment and prevention of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and others. Retinoids are necessary for the functioning of the immune system and are powerful immunomodulators. Additionally, retinoids have the potential for the therapy of various proliferative diseases.

Conclusion

Conclusion. Long-term studies of the pharmacological activity of retinoic acid and its structural analogs aim to investigate and establish the precise mechanisms of their actions, as well as their involvement in the pathogenesis of various diseases. The synthesis of retinoids aims to design compounds with high selectivity towards specific receptors, which would exclude the multitarget action of natural regulatory molecules and the associated side effects. Synthetic retinoids devoid of teratogenic and other side effects can find application as therapeutic agents for the treatment of metabolic disorders, various malignancies, as well as kidney, lung, and CNS diseases. Furthermore, the development of prodrugs based on retinoids with controlled release of active molecules is also a promising direction in this field of medicinal chemistry.  

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