В журнале Pharmaceutics (IF=5,4) опубликована статья с участием сотрудников Института: к.х.н. С.О. Куранова (нс, ЛФАВ), Д.А. Понькиной (мнс ЛФИ), Ю.В. Мешковой (мнс ЛИВП), к.б.н. М.К. Марениной (нс ЛИВП), д.м.н. Н.А. Жуковой (внс, ЛФИ)д.б.н. М.В. Хвостова (завлаб ЛИВП), д.б.н., проф. Т.Г. Толстиковой (завлаб ЛФИ), д.х.н. О.А. Лузиной (внс ЛФАВ) и д.х.н., проф., чл.-корр. РАН Н.Ф. Салахутдинова (зав. отделом Медицинской химии):
Bornyl-Containing Derivatives of Benzyloxyphenylpropanoic Acid as FFAR1 Agonists: In Vitro and In Vivo Studies
Darya A. Pon’kina, Sergey O. Kuranov, Mariya K. Marenina, Yulia V. Meshkova, Nataliya A. Zhukova, Mikhail V. Khvostov , Olga A. Luzina, Tatiana G. Tolstikova and Nariman F. Salakhutdinov
Pharmaceutics 2023, 15(6), 1670;
Publication Date:07 Jun 2023
https://doi.org/10.3390/pharmaceutics15061670
(This article belongs to the Special Issue Diabetes Mellitus: Promising Molecules, Drug Modification, Formulations, and Therapy)
Abstract
Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide. Several classes of hypoglycemic drugs are used to treat it, but various side effects limit their clinical use. Consequently, the search for new anti-diabetic agents remains an urgent task for modern pharmacology. In this investigation, we examined the hypoglycemic effects of bornyl-containing benzyloxyphenylpropanoic acid derivatives (QS-528 and QS-619) in a diet-induced model of T2DM. Animals were given the tested compounds per os at a dose of 30 mg/kg for 4 weeks. At the end of the experiment, compound QS-619 demonstrated a hypoglycemic effect, while QS-528 showed hepatoprotection. In addition, we performed a number of in vitro and in vivo experiments to study the presumed mechanism of action of the tested agents. Compound QS-619 was determined to activate the free fatty acid receptor-1 (FFAR1) similarly to the reference agonist GW9508 and its structural analogue QS-528. Both agents also increased insulin and glucose-dependent insulinotropic polypeptide concentrations in CD-1 mice. Our results indicate that QS-619 and QS-528 are probably full FFAR1 agonists.
Keywords:
bornyl derivatives; FFAR1 agonist; hypoglycemic activity; hepatoprotective effect; OGTT; diabetes mellitus
Альметрики:
Метрики PlumX теперь доступны в Scopus: узнайте, как другие ученые используют ваши исследования