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"10.29235/1561-8331-2021-57-4-456-462vestich-689Research ArticleБИООРГАНИЧЕСКАЯ ХИМИЯBIOORGANIC CHEMISTRYСинтез новых тиазоло[3,2-а]пиримидинов и in silico анализ их биоактивностиSynthesis of new thiazolo[3,2-a]pyrimidine derivatives and in silico analysis of their bioactivityМинееваИ. В.MineevaI. V.

Минеева Ирина Владимировна – канд. хим. наук, доцент, докторант кафедры органической химии

пр. Независимости, 4, 220030, Минск, Республика Беларусь

Iryna V. Mineeva – Ph. D. (Chemistry), Associate Professor, Doctoral Student of the Department of Organic Chemistry

14, Leningradskaya Str., 220006, Minsk, Republic of Belarus

i.mineyeva@yandex.ruФалетровЯ. В.FaletrovY. V.

Фалетров Ярослав Вячеславович – канд. хим. наук, доцент, докторант кафедры высокомолекулярных соединений, вед. науч. сотрудник

ул. Ленинградская, 14, 220006, Минск, Республика Беларусь

Yaroslav V. Faletrov – Ph. D. (Chemistry), Associate Professor, Doctoral Student of the Department of Macromolecular Compounds, Leading Researcher

14, Leningradskaya Str., 220006, Minsk, Republic of Belarus

yaroslav82@tut.byСтаровойтоваВ. А.StarovoytovaV. A.

Старовойтова Виктория Александровна – стажер мл. науч. сотрудник

ул. Ленинградская, 14, 220006, Минск, Республика Беларусь

Victoria A. Starovoytova – Research Assistant

14, Leningradskaya Str., 220006, Minsk, Republic of Belarus

vika.starovoytova.2000@mail.ruШкуматовВ. М.ShkumatovV. M.

Шкуматов Владимир Макарович – член-корреспондент, д-р биол. наук, профессор, зав. лаб.

ул. Ленинградская, 14, 220006, Минск, Республика Беларусь

Vladimir M. Shkumatov – Corresponding Member of the National Academy of Sciences of Belarus, D. Sc. (Biology), Professor, Head of the Laboratory

14, Leningradskaya Str., 220006, Minsk, Republic of Belarus

vlad.shkumatov@tut.byБелорусский государственный университетBelarusian State UniversityБелорусский государственный университет; Научно-исследовательский институт физико-химических проблем БГУBelarusian State University; Research Institute for Physical Chemical Problems of the Belarusian State UniversityНаучно-исследовательский институт физико-химических проблем БГУResearch Institute for Physical Chemical Problems of the Belarusian State University202103122021574456462Copyright © Минеева И.В., Фалетров Я.В., Старовойтова В.А., Шкуматов В.М., 20212021Минеева И.В., Фалетров Я.В., Старовойтова В.А., Шкуматов В.М.Mineeva I.V., Faletrov Y.V., Starovoytova V.A., Shkumatov V.M.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/689

Разработан эффективный метод получения и синтезированы новые тиазоло[3,2-a]пиримидины, содержащие н-пентановый или β-гидроксициклопропановый, а также флуоресцирующий бензо[f]кумариновый заместители с выходами более 60 %. Компьютерными методами (in silico) показана способность полученных соединений проникать через липидный бислой и оценено их сродство к ряду протеинкиназ (соединения 4 и 6 связываются с протеинкиназой AKT1 с кодом PDB 3о96; величины, рассчитываемые программой Autodock Vina энергии связывания (Ebind), составили: -10,9 и -10,6 ккал/моль), ацетилхолинэстеразе и цитохромам P450 человека (для цитохрома P450 3A4, pdb 5vcd, Ebind -12,3 ккал/моль).

An effective method of synthesis thiazolo[3,2-a]pyrimidine derivatives was developed and the compounds with n-pentyl or β-acetoxycyclopropyl as well as fluorescent benzo[f]coumarin substituents were obtained with yields 60 % and more. Using computational (in silico) approaches we demonstrated the ability of the obtained compounds to permeate lipid bilayer as well as their affinity to some protein kinases (compounds 4 and 6 bind with a protein kinase AKT1 with PDB code 3о96; Autodock Vina-computed energy of binding (Ebind) values were -10.9 and -10.6 kcal/mol, respectively), acethylcholine esterase and some human cytochromes P450 (for P450 3A4, pdb 5vcd, Ebind -12.3 kcal/mol).

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