Ukr.Biochem.J. 2019; Том 91, № 4, липень-серпень, c. 5-16

doi: https://doi.org/10.15407/ubj91.04.005

1,3-Оксазол-4-ілфосфонієві солі як новий клас непептидних інгібіторів фурину

26.07.2019   Uncategorized   No comments

Т. В. Осадчук1, В. К. Кібірєв1,2, О. В. Шибирин1, А. В. Семироз1,
Є. С. Велігіна1, Е. Р. Абдурахманова1, В. С. Броварець1

1Інститут біоорганічної хімії та нафтохімії ім. В. П. Кухаря НАН України, Київ;
e-mail: brovarets@bpci.kiev.ua;
2Інститут біохімії ім. О. В. Палладіна НАН України, Київ

Отримано: 22 лютого 2019; Затверджено: 17 травня 2019

Синтезовано низку нових похідних 1,3-оксазол-4-ілфосфонієвих солей, які містять у С2- та С5-положеннях гетероциклу електронодонорні або електроноакцепторні групи. Сполуки охарактеризовано 1Н, 31Р ЯМР- та ІЧ-спектроскопією, даними елементного аналізу та хромато-масспектрометрії. Знайдено, що ці азоли є новим класом непептидних інгібіторів фурину. Залежно від хімічної будови вони інактивують ензим за механізмом конкурентного, неконкурентного або змішаного інгібування. Оцінка синтезованих похідних як інгібіторів фурину показала, що серед трифенілфосфонієвих солей оксазол 12, який містить у С2-положенні 2,4-дихлорфеніл-, а у С5 – MeS-групу, є найактивнішим (Kі = 1,57 мкМ) конкурентним інгібітором ензиму. Результати свідчать про те, що хімічна модифікація фосфонієвих похідних оксазолу може бути корисною для створення потужніших та селективних інгібіторів фурину.

Ключові слова: , , , , ,

Посилання:

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