danДоклады Национальной академии наук БеларусиDoklady of the National Academy of Sciences of Belarus1561-83232524-2431The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8323-2018-62-3-281-292dan-519Research ArticleХИМИЯCHEMISTRYКОМПЬЮТЕРНЫЙ ДИЗАЙН ПОТЕНЦИАЛЬНЫХ ИНГИБИТОРОВ АРОМАТАЗЫ НА ОСНОВЕ ПРОИЗВОДНЫХ 1,2,4-ТРИАЗОЛАCOMPUTER-AIDED DESIGN OF POTENTIAL AROMATASE INHIBITORS BASED ON 1,2,4-TRIAZOLE DERIVATIVESАндриановА. М.AndrianovA. M.

Андрианов Александр Михайлович – д-р хим. наук, гл. науч. сотрудник.

ул. Купревича, 5/2, 220141, Минск.

Andrianov Alexander Mikhailovich – D. Sc. (Chemistry), Chief researcher. 

5/2, Kuprevich Str., 220141.

andrianov@iboch.bas-net.byНиколаевГ. И.NikolaevG. I.

Николаев Григорий Игоревич – аспирант.

ул. Сурганова, 6, 220012, Минск.

Nikolaev Gregory Igorevich – Postgraduate student. 

6, Surganov Str., 220072, Minsk.

reshaemvsem@gmail.comКашинИ. А.KashynI. A.

Кашин Иван Александрович – канд. хим. наук, ст. науч. сотрудник.

ул. Сурганова, 6, 220012, Минск.

Kashyn Ivan Aleksandrovich – Ph. D. (Chemistry), Senior researcher.

6, Surganov Str., 220072, Minsk.

lighkia@gmail.comКорноушенкоЮ. В.KornoushenkoYu. V.

Корноушенко Юрий Валерьевич – канд. хим. наук, ст. науч. сотрудник.

ул. Купревича, 5/2, 220141, Минск.

Kornoushenko Yury Valerievich – Ph. D. (Chemistry), Senior researcher. 

5/2, Kuprevich Str., 220141, Minsk.

kornoushenko@iboch.bas-net.byУсановС. А.UsanovS. A.

Усанов Сергей Александрович – член-корреспондент, д-р хим. наук, профессор. 

ул. Купревича, 5/2, 220141, Минск.

Usanov Sergey Aleksandrovich – Corresponding Member, D. Sc. (Chemistry), Professor.

5/2, Kuprevich Str., 220141, Minsk.

usanov@iboch.bas-net.byИнститут биоорганической химии Национальной академии наук Беларуси.РоссияInstitute of Bioorganic Chemistry of the National Academy of Sciences of Belarus.Russian FederationОбъединенный институт проблем информатики Национальной академии наук Беларуси.РоссияUnited Institute of Informatics Problems of the National Academy of Sciences of Belarus.Russian FederationОбъединенный институт проблем информатики Национальной академии наук Беларуси.РоссияUnited Institute of Informatics Problems of the National Academy of Sciences of Belarus .Russian FederationИнститут биоорганической химии Национальной академии наук Беларуси.РоссияInstitute of Bioorganic Chemistry of the National Academy of Sciences of BelarusRussian FederationИнститут биоорганической химии Национальной академии наук Беларуси.РоссияInstitute of Bioorganic Che mistry of the National Academy of Sciences of BelarusRussian Federation201828062018623281292Copyright © Андрианов А.М., Николаев Г.И., Кашин И.А., Корноушенко Ю.В., Усанов С.А., 20182018Андрианов А.М., Николаев Г.И., Кашин И.А., Корноушенко Ю.В., Усанов С.А.Andrianov A.M., Nikolaev G.I., Kashyn I.A., Kornoushenko Y.V., Usanov S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://doklady.belnauka.by/jour/article/view/519

Методами молекулярного моделирования осуществлен компьютерный дизайн высокоаффинных ингибиторов ароматазы на основе производных 1,2,4-триазола. С помощью молекулярного докинга и квантовой химии проведена оценка потенциальной биологической активности сконструированных соединений. В результате идентифицированы шесть соединений-лидеров, которые образуют координационную связь с атомом железа гема фермента и эффективно взаимодействуют c его субстрат-связывающим сайтом. Выполнен анализ межмолекулярc его субстрат-связывающим сайтом. Выполнен анализ межмолекуляр его субстрат-связывающим сайтом. Выполнен анализ межмолекулярных взаимодействий, реализующихся в структурных комплексах этих лигандов с ароматазой, и рассчитаны энтальпии их образования. На основе полученных данных предсказано, что идентифицированные соединения формируют перспективные базовые структуры для разработки новых эффективных лекарственных препаратов для терапии рака молочной железы.

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