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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">actabiomedica</journal-id><journal-title-group><journal-title xml:lang="ru">Acta Biomedica Scientifica</journal-title><trans-title-group xml:lang="en"><trans-title>Acta Biomedica Scientifica</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2541-9420</issn><issn pub-type="epub">2587-9596</issn><publisher><publisher-name>Scientific Centre for Family Health and Human Reproduction Problems</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29413/ABS.2024-9.1.12</article-id><article-id custom-type="elpub" pub-id-type="custom">actabiomedica-4606</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОФТАЛЬМОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>OPHTHALMOLOGY</subject></subj-group></article-categories><title-group><article-title>Виртуальный и  экспериментальный скрининг новых биоизостеров мелатонина для  лечения глаукомы</article-title><trans-title-group xml:lang="en"><trans-title>Virtual and  experimental screening of new melatonin bioisosteres for the treatment of glaucoma</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9645-3324</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бабков</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Babkov</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бабков Денис Александрович – кандидат химических наук, старший научный сотрудник лаборатории метаботропных лекарственных средств Научного центра инновационных лекарственных средств, </p><p>400131, г. Волгоград, пл. Павших Борцов, 1</p></bio><bio xml:lang="en"><p>Denis  A. Babkov – Cand.  Sc. (Chem.), Senior Research Officer at the  Laboratory of  Metabotropic Agents of  the Scientific Сentre for Innovative Drugs,</p><p>Pavshikh Bortsov square 1, Volgograd 400131</p></bio><email xlink:type="simple">dababkov@volgmed.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8477-254X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Таран</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Taran</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Таран Алёна Сергеевна – кандидат медицинских наук, старший научный сотрудник лаборатории токсикологии Научного центра инновационных лекарственных средств;</p><p>младший научный сотрудник лаборатории экспериментальной фармакологии, 400131, г. Волгоград, пл. Павших Борцов, 1</p></bio><bio xml:lang="en"><p>Alena S. Taran – Cand. Sc. (Med.), Senior Research Officer at the Laboratory of Toxicology of the Scientific Сentre for Innovative Drugs;</p><p>Junior Research Officer at the Laboratory of Experimental Pharmacology,</p><p>Pavshikh Bortsov square 1, Volgograd 400131</p></bio><email xlink:type="simple">alena-beretta-taran@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шевченко</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Shevchenko</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шевченко Алина Андреевна – аспирант кафедры фармакологии и биоинформатики, </p><p>400131, г. Волгоград, пл. Павших Борцов, 1</p></bio><bio xml:lang="en"><p>Alina A. Shevchenko – Postgraduate at the Department of Pharmacology and Bioinformatics, </p><p>Pavshikh Bortsov square 1, Volgograd 400131</p></bio><email xlink:type="simple">alina.shew4enko2014@yandex.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2119-4233</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Науменко</surname><given-names>Л. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Naumenko</surname><given-names>L. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Науменко Людмила Владимировна – доктор медицинских наук, профессор кафедры фармакологии и биоинформатики, </p><p>400131, г. Волгоград, пл. Павших Борцов, 1</p></bio><bio xml:lang="en"><p>Lyudmila V. Naumenko – Dr.  Sc. (Med.), Professor at  the  Department of  Pharmacology and  Bioinformatics,</p><p>Pavshikh Bortsov square 1, Volgograd 400131</p></bio><email xlink:type="simple">milanaumenko@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9928-694X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Жуковская</surname><given-names>О. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Zhukovskaya</surname><given-names>O. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Жуковская Ольга Николаевна – кандидат химических наук, старший научный сотрудник лаборатории органического синтеза, </p><p>344090, г. Ростов-на-Дону, просп. Стачки, 194/2</p></bio><bio xml:lang="en"><p>Olga N. Zhukovskaya – Cand. Sc. (Chem.), Senior Research Officer at the Laboratory of Organic Synthesis, </p><p>Stachki Ave. 194/2, Rostov-on-Don 344090</p></bio><email xlink:type="simple">zhukowskaia.ol@yandex.ru</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1777-7081</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ефремов</surname><given-names>А. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Efremov</surname><given-names>A. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ефремов Александр Михайлович – аспирант кафедры медицинской химии и тонкого органического синтеза, </p><p>119991, г. Москва, Ленинские горы, 1</p></bio><bio xml:lang="en"><p>Alexander M. Efremov – Postgraduate at  the Department of  Medicinal Chemistry and  Fine Organic Synthesis,</p><p>Leninskie Gory 1, Moscow 119991</p></bio><email xlink:type="simple">sash-ka.e@yandex.ru</email><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9804-5447</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Безсонова</surname><given-names>Е. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Bezsonova</surname><given-names>E. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Безсонова Елена Николаевна – аспирант кафедры медицинской химии и тонкого органического синтеза, </p><p>119991, г. Москва, Ленинские горы, 1</p></bio><bio xml:lang="en"><p>Elena N. Bezsonova – Postgraduate at the Department of Medicinal Chemistry and Fine Organic Synthesis,</p><p>Leninskie Gory 1, Moscow 119991</p></bio><email xlink:type="simple">elena.bezsonova@chemistry.msu.ru</email><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2518-3694</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лозинская</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Lozinskaya</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Лозинская Наталья Александровна – кандидат химических наук, доцент кафедры медицинской химии и тонкого органического синтеза, </p><p>119991, г. Москва, Ленинские горы, 1</p></bio><bio xml:lang="en"><p>Natalia  A. Lozinskaya – Cand.  Sc. (Chem.), Associate Professor at  the Department of  Medicinal Chemistry and  Fine Organic Synthesis, </p><p>Leninskie Gory 1, Moscow 119991</p></bio><email xlink:type="simple">natalylozinskaya@mail.ru</email><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7185-4826</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Спасов</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Spasov</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Спасов Александр Алексеевич – доктор медицинских наук, заведующий кафедрой фармакологии и биоинформатики;</p><p>заведующий отделом фармакологии, заведующий лабораторией экспериментальной фармакологии, 400131, г. Волгоград, пл. Павших Борцов, 1</p></bio><bio xml:lang="en"><p>Alexander A. Spasov – Dr. Sc. (Med.), Head of the Department of Pharmacology and Bioinformatics,</p><p>Head of the Department of Pharmacology, Head of the Laboratory of Experimental Pharmacology,</p><p>Pavshikh Bortsov square 1, Volgograd 400131</p></bio><email xlink:type="simple">aspasov@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Волгоградский государственный медицинский университет» Минздрава России</institution></aff><aff xml:lang="en"><institution>Volgograd State Medical University</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБОУ ВО «Волгоградский государственный медицинский университет» Минздрава России;&#13;
ГБУ «Волгоградский медицинский научный центр»</institution></aff><aff xml:lang="en"><institution>Volgograd State Medical University;&#13;
Volgograd Medical Scientific Center</institution></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ГБУ «Волгоградский медицинский научный центр»</institution></aff><aff xml:lang="en"><institution>Volgograd Medical Scientific Center</institution></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>Научно-исследовательский институт физической и органической химии, ФГАОУ ВО «Южный федеральный университет»</institution></aff><aff xml:lang="en"><institution>Research Scientific Institute of Physical and Organic Chemistry, Southern Federal University</institution></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru"><institution>ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»</institution></aff><aff xml:lang="en"><institution>Lomonosov Moscow State University</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>26</day><month>03</month><year>2024</year></pub-date><volume>9</volume><issue>1</issue><fpage>116</fpage><lpage>128</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Бабков Д.А., Таран А.С., Шевченко А.А., Науменко Л.В., Жуковская О.Н., Ефремов А.М., Безсонова Е.Н., Лозинская Н.А., Спасов А.А., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Бабков Д.А., Таран А.С., Шевченко А.А., Науменко Л.В., Жуковская О.Н., Ефремов А.М., Безсонова Е.Н., Лозинская Н.А., Спасов А.А.</copyright-holder><copyright-holder xml:lang="en">Babkov D.A., Taran A.S., Shevchenko A.A., Naumenko L.V., Zhukovskaya O.N., Efremov A.M., Bezsonova E.N., Lozinskaya N.A., Spasov A.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.actabiomedica.ru/jour/article/view/4606">https://www.actabiomedica.ru/jour/article/view/4606</self-uri><abstract><sec><title>Обоснование</title><p>Обоснование. Мелатонин является эндогенным регулятором внутриглазного давления (ВГД), но  эффективность его  применения в  качестве лекарственного средства при глаукоме ограничена.</p></sec><sec><title>Цель исследования</title><p>Цель исследования. Разработка и валидация метода виртуального скрининга для выявления биоизостерических аналогов мелатонина, перспективных для изучения в качестве средств, снижающих внутриглазное давление.</p></sec><sec><title>Результаты</title><p>Результаты. Была создана база данных, содержащая информацию о структуре и экспериментальном сродстве 48 отдельных эталонных соединений. Оценка риска мутагенной, канцерогенной, раздражающей и репродуктивной токсичности была выполнена в  DataWarrior на  основе подструктурного анализа и  идентификации фрагментов, которые являются маркерами соответствующей токсичности. Был проведён виртуальный скрининг 2457 структур и 25 соединений из числа отобранных были экспериментально изучены на предмет их влияния на ВГД у интактных крыс. Было обнаружено, что 10 из 25 приоритизированных соединений способны значимо снижать ВГД; соединение RU-398 снижало уровень ВГД на 40 %, K-165 – на 40,9 %, а RU-615 снижало глаукому на 33,3 %.</p></sec><sec><title>Заключение</title><p>Заключение. Результативность виртуального скрининга после экспериментальной валидации составила 40 %. Выявленные активные соединения являются перспективными для дальнейшего изучения и разработки в качестве средств для лечения глаукомы.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background. Melatonin is an endogenous regulator of intraocular pressure (IOP), but its effectiveness as a drug for glaucoma treatment is limited.</p></sec><sec><title>The  aim of  the  study</title><p>The  aim of  the  study. To develop and  to  validate a  virtual screening method to identify bioisosteric analogs of melatonin that are promising for study as agents that reduce intraocular pressure.</p></sec><sec><title>Results</title><p>Results. A database containing structural and experimental affinity information for 48 individual reference compounds was created. Risk assessments for mutagenic, carcinogenic, irritant and reproductive toxicity were performed in DataWarrior based on substructural analysis and identification of fragments that are markers of relevant toxicity. A virtual screening of 2457 structures was carried out and 25 compounds from the selected ones were experimentally studied for their effect on intraocular pressure (IOP) in intact rats. 10 of the 25 prioritized compounds were found to significantly reduce IOP; compound RU-398 reduced IOP by 40 %, K-165 – by 40.9 %, and RU-615 reduced glaucoma by 33.3 %.</p></sec><sec><title>Conclusion</title><p>Conclusion. The  effectiveness of  virtual screening after experimental validation was 40 %. The identified active compounds are promising for further study and development as the agents for the treatment of glaucoma.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>изостер</kwd><kwd>мелатонин</kwd><kwd>глаукома</kwd><kwd>внутриглазное давление</kwd><kwd>виртуальный скрининг</kwd></kwd-group><kwd-group xml:lang="en"><kwd>isostere</kwd><kwd>melatonin</kwd><kwd>glaucoma</kwd><kwd>intraocular pressure</kwd><kwd>virtual screening</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследования выполнены в  рамках регионального проекта Российского научного фонда от 25.03.2022 № 22-15-20025 «Синтез и исследование эффективности биоизостеров мелатонина».</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Stein JD, Khawaja AP, Weizer JS. 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