PMID- 37376118
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230701
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 6
DP  - 2023 Jun 7
TI  - Bornyl-Containing Derivatives of Benzyloxyphenylpropanoic Acid as FFAR1 Agonists: 
      In Vitro and In Vivo Studies.
LID - 10.3390/pharmaceutics15061670 [doi]
LID - 1670
AB  - 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.
FAU - Pon'kina, Darya A
AU  - Pon'kina DA
AUID- ORCID: 0009-0009-0796-608X
AD  - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of 
      the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 
      630090, Russia.
FAU - Kuranov, Sergey O
AU  - Kuranov SO
AUID- ORCID: 0000-0003-1711-7945
AD  - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of 
      the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 
      630090, Russia.
FAU - Marenina, Mariya K
AU  - Marenina MK
AUID- ORCID: 0000-0002-9500-1713
AD  - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of 
      the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 
      630090, Russia.
FAU - Meshkova, Yulia V
AU  - Meshkova YV
AUID- ORCID: 0000-0002-5935-2540
AD  - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of 
      the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 
      630090, Russia.
FAU - Zhukova, Nataliya A
AU  - Zhukova NA
AD  - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of 
      the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 
      630090, Russia.
FAU - Khvostov, Mikhail V
AU  - Khvostov MV
AUID- ORCID: 0000-0002-5906-4223
AD  - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of 
      the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 
      630090, Russia.
FAU - Luzina, Olga A
AU  - Luzina OA
AUID- ORCID: 0000-0001-8627-3453
AD  - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of 
      the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 
      630090, Russia.
FAU - Tolstikova, Tatiana G
AU  - Tolstikova TG
AD  - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of 
      the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 
      630090, Russia.
FAU - Salakhutdinov, Nariman F
AU  - Salakhutdinov NF
AD  - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of 
      the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 
      630090, Russia.
LA  - eng
GR  - 21-73-00246/Russian Science Foundation/
PT  - Journal Article
DEP - 20230607
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC10300945
OTO - NOTNLM
OT  - FFAR1 agonist
OT  - OGTT
OT  - bornyl derivatives
OT  - diabetes mellitus
OT  - hepatoprotective effect
OT  - hypoglycemic activity
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses or interpretation of data; in 
      the writing of the manuscript; or in the decision to publish the results.
EDAT- 2023/06/28 06:42
MHDA- 2023/06/28 06:43
PMCR- 2023/06/07
CRDT- 2023/06/28 01:37
PHST- 2023/03/27 00:00 [received]
PHST- 2023/05/12 00:00 [revised]
PHST- 2023/06/02 00:00 [accepted]
PHST- 2023/06/28 06:43 [medline]
PHST- 2023/06/28 06:42 [pubmed]
PHST- 2023/06/28 01:37 [entrez]
PHST- 2023/06/07 00:00 [pmc-release]
AID - pharmaceutics15061670 [pii]
AID - pharmaceutics-15-01670 [pii]
AID - 10.3390/pharmaceutics15061670 [doi]
PST - epublish
SO  - Pharmaceutics. 2023 Jun 7;15(6):1670. doi: 10.3390/pharmaceutics15061670.