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"10.29235/1561-8331-2023-59-1-42-48vestich-788Research ArticleБИООРГАНИЧЕСКАЯ ХИМИЯBIOORGANIC CHEMISTRYАфіннасць Рывараксабану in silico да β-кетаацыл[АСР]сінтазы І: пошук новага фармакафораIn silico Rivaroxaban binding affinity to β-ketoacyl[ACP]synthase I: search for new pharmacophoreЛахвічТ. Т.LakhvichT. T.

Лахвич Тодар Тодаравіч – канд. хім. навук, дацэнт

пр. Дзяржынскага, 83, 220116, Мінск

Lakhvich Todar T. – Ph. D. (Chemistry), Associate Professor

83, Dzerzhinski Ave., 220083, Minsk

lakhvichtt@gmail.comРынейскаяВ. М.RyneiskayaV. M.

Рынейская Вольга Мікалаеўна – канд. мед. навук,дацэнт, загадчык кафедры

пр. Дзяржынскага, 83, 220116, Мінск

Ryneiskaya Volha М. – Ph. D. (Medicine), AssociateProfessor, Head of the Department

83, Dzerzhinski Ave., 220083, Minsk

ryneiskaya@mail.ruБеларускі дзяржаўны медыцынскі ўніверсітэтBelarusian State Medical University2023050320235914248Copyright © Лахвіч Т.Т., Рынейская В.М., 20232023Лахвіч Т.Т., Рынейская В.М.Lakhvich T.T., Ryneiskaya 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/788

Даследавана in silico актыўнасць Рывараксабану як прадстаўніка аксазалідзінонаў у дачыненні да β-кетаацыл[АСР]сінтазы І. Пры дапамозе метадаў малекулярнага докінгу вызначаныя цэнтры звязвання Рывараксабану з пратэінам. Для цэнтра, які забяспечвае найбольшую афіннасць Рывараксабану з пратэінам, былі прааналізаваны 4 кластары, якія характарызуюцца лікам прабегаў больш за 15. Выяўлена, што канкрэтная пазіцыя ліганда ў межах гэтых кластараў можа мяняцца падчас рэалізацыі механізму, які забяспечвае фізіялагічны водгук. Пры гэтым нязначныя змены характарыстык асяроддзя могуць прывесці да пераходу ад энергетычна дамінантнай пазіцыі (Езв = –10,26 ккал/моль; з пераважна гідрафобным характарам ўзаемадзеянняў) да іншай пазіцыі (Езв. = –8,88 ккал/моль) з пераважна гідрафільным характарам ўзаемадзеянняў. Такі дынамічны пераход можа спрычыняць фізіялагічны водгук. Вынікі даследавання з вялікай ступенню верагоднасці пацвярджаюць рэалізацыю адмысловага механізму антымікабактэрыяльнага дзеяння Рывараксабану праз інгібаванне сінтэзу міколавых кіслот.

The activity of Rivaroxaban as a representative of oxazolidinone series in relation to β-ketoacyl[ACP]synthase I has been studied in silico. Using the molecular docking methods, the binding sites of Rivaroxaban with protein have been identified. For the site providing the highest affinity of Rivaroxaban with protein (-10.26 kcal/mol), 4 clusters characterized by a number of runs greater than 15 have been analyzed. It was found that the specific position of the ligand within these clusters can be changed via mechanism providing a physiological response. Slight changes in the characteristics of the environment can lead to a transition from an energetically dominant position (BE = –10.26 kcal/mol) with predominantly hydrophobic interactions to another position (BE = –8.88 kcal/mol) with predominantly hydrophilic interactions. Dynamic transition discussed may cause a physiological response. The results of the study with a high degree of probability confirm the implementation of a specific mechanism of antimycobacterial action of Rivaroxaban through inhibition of the mycolate biosynthesis.

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