TY - JOUR

T1 - Isopimaric Acid Derivatives as Potential Dual PPARα/γ Agonists in the Treatment of Metabolic Syndrome

AU - Blokhin, Mikhail E.

AU - Borisov, Sergey A.

AU - Gromova, Mariia A.

AU - Meshkova, Yulia V.

AU - Zhukova, Nataliya A.

AU - Nikonova, Sophia V.

AU - Zhurakovsky, Igor P.

AU - Luzina, Olga A.

AU - Khvostov, Mikhail V.

AU - Kudlay, Dmitry A.

AU - Salakhutdinov, Nariman F.

N1 - This research was funded by the Russian Scientific Foundation project No. 24-25-00120. Isopimaric Acid Derivatives as Potential Dual PPARα/γ Agonists in the Treatment of Metabolic Syndrome / M. E. Blokhin, S. A. Borisov, M. A. Gromova, Y. V. Meshkova, N. A. Zhukova, S. V. Nikonova, I. P. Zhurakovsky, O. A. Luzina, M. V. Khvostov, D. A. Kudlay, N. F. Salakhutdinov // Scientia Pharmaceutica. - 2025. - Т. 93. № 3. - № 44. DOI 10.3390/scipharm93030044

PY - 2025/9/5

Y1 - 2025/9/5

N2 - Metabolic syndrome is characterized by a group of metabolic disorders that can lead to the development of cardiovascular diseases, obesity and type 2 diabetes mellitus (T2DM). Nowadays, there are several groups of drugs for the treatment of T2DM, but there is no one that would not have significant side effects and suitable for most patients. In our previous study, it was shown that the (S)-2-ethoxy-3-phenylpropanoic acid derivative containing isopimaric acid moiety exhibited pronounced antidiabetic activity. In the present study, a series of (S)-2-ethoxy-3-phenylpropanoic acid derivatives containing an isopimaric acid moiety with various aromatic substituents at position 16 were synthesized. The synthesized compounds were tested for their ability to improve glycemic control and to counter lipid abnormalities in C57BL/6Ay mice placed on a high-fat/high-cholesterol diet. Of all tested compounds, the 2-NO2-phenyl derivative (16d) had the most pronounced effect in decreasing blood glucose and serum triglyceride levels. All the compounds displayed a relatively safe profile in the animal studies carried out in this work. Therefore, it can be concluded that chemical modification of isopimaric acid may enhance its efficacy as an antidiabetic agent as part of the potential glitazar.

AB - Metabolic syndrome is characterized by a group of metabolic disorders that can lead to the development of cardiovascular diseases, obesity and type 2 diabetes mellitus (T2DM). Nowadays, there are several groups of drugs for the treatment of T2DM, but there is no one that would not have significant side effects and suitable for most patients. In our previous study, it was shown that the (S)-2-ethoxy-3-phenylpropanoic acid derivative containing isopimaric acid moiety exhibited pronounced antidiabetic activity. In the present study, a series of (S)-2-ethoxy-3-phenylpropanoic acid derivatives containing an isopimaric acid moiety with various aromatic substituents at position 16 were synthesized. The synthesized compounds were tested for their ability to improve glycemic control and to counter lipid abnormalities in C57BL/6Ay mice placed on a high-fat/high-cholesterol diet. Of all tested compounds, the 2-NO2-phenyl derivative (16d) had the most pronounced effect in decreasing blood glucose and serum triglyceride levels. All the compounds displayed a relatively safe profile in the animal studies carried out in this work. Therefore, it can be concluded that chemical modification of isopimaric acid may enhance its efficacy as an antidiabetic agent as part of the potential glitazar.

KW - hypoglycemic activity

KW - isopimaric acid

KW - metabolic syndrome

KW - natural compounds

KW - type 2 diabetes mellitus

UR - https://www.mendeley.com/catalogue/450076fd-a66e-3b9e-a3ad-2ac62c815b0f/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105017132124&origin=inward

U2 - 10.3390/scipharm93030044

DO - 10.3390/scipharm93030044

M3 - Article

VL - 93

JO - Scientia Pharmaceutica

JF - Scientia Pharmaceutica

SN - 2218-0532

IS - 3

M1 - 44

ER -