Bornyl-Containing Derivatives of Benzyloxyphenylpropanoic Acid as FFAR1 Agonists: In Vitro and In Vivo Studies

Bornyl-Containing Derivatives of Benzyloxyphenylpropanoic Acid as FFAR1 Agonists: In Vitro and In Vivo Studies Full article

Journal

Pharmaceutics
ISSN: 1999-4923

Output data

Year: 2023, Volume: 15, Number: 6, Pages: 1670 Pages count : 1 DOI: 10.3390/pharmaceutics15061670

Tags

bornyl derivatives; FFAR1 agonist; hypoglycemic activity; hepatoprotective effect; OGTT; diabetes mellitus

Authors

Pon’kina Darya A. ¹ , Kuranov Sergey O. ¹ , Marenina Mariya K. ¹ , Meshkova Yulia V. ¹ , Zhukova Nataliya A. ¹ , Khvostov Mikhail V. ¹ , Luzina Olga A. ¹ , Tolstikova Tatiana G. ¹ , Salakhutdinov Nariman F. ¹

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of Siberian Branch of Russian Academy of Sciences

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.

Pon’kina D.A. , Kuranov S.O. , Marenina M.K. , Meshkova Y.V. , Zhukova N.A. , Khvostov M.V. , Luzina O.A. , Tolstikova T.G. , Salakhutdinov N.F.
Bornyl-Containing Derivatives of Benzyloxyphenylpropanoic Acid as FFAR1 Agonists: In Vitro and In Vivo Studies
Pharmaceutics. 2023. V.15. N6. P.1670. DOI: 10.3390/pharmaceutics15061670 WOS Scopus РИНЦ OpenAlex

Submitted:	Mar 27, 2023
Accepted:	Jun 2, 2023
Published print:	Jun 7, 2023

Web of science:	WOS:001015678100001
Scopus:	2-s2.0-85163758587
Elibrary:	61770142
OpenAlex:	W4380051253

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