TY - JOUR

T1 - Hypoglycemic and Analgesic Effects of Benzyloxyphenylpropanoic Derivatives of Isobornylamine as FFAR-1 Agonists

AU - Elkina, Mariya A

AU - Khvostov, Mikhail V

AU - Kuranov, Sergey O

AU - Luzina, Olga A

AU - Zhukova, Natalia A

AU - Meshkova, Yulia V

AU - Tolstikova, Tatiana G

AU - Salakhutdinov, Nariman F

N1 - © 2025 Deutsche Pharmazeutische Gesellschaft.

PY - 2025/11

Y1 - 2025/11

N2 - Type 2 diabetes mellitus (T2DM) is considered the "pandemic of the 21st century." It is a complex multifactorial disease associated with chronic hyperglycemia, causing further complications that result in disability and early mortality. Due to the fact that the main focus of T2DM therapy is to reduce the patient's blood sugar levels, avoiding drug-induced hypoglycemia is important. Free fatty acid receptor 1 (FFAR1) agonists are considered promising hypoglycemic agents without the risk of hypoglycemia. In the future, FFAR1 agonists may expand the range of safer hypoglycemic agents with a mechanism of action not currently used in T2DM therapy. In this study, the hypoglycemic effect of a novel and potent FFAR1 agonist based on benzyloxyphenylpropanoic acid's core containing an aminobornyl fragment was investigated in a long-term experiment on C57BL/6 Ay/a (Agouti Yellow) mice. The results demonstrated a reduction in insulin resistance, attributed to the hepatoprotective effect of the compound. Additionally, the analgesic effect of the compound was evaluated in experimental pain models. It appeared that the compound exhibited a moderate analgesic effect at high doses. Furthermore, the FFAR1-mediated mechanism of action was confirmed through experiments with an FFAR1 antagonist coadministration, which suppressed both hypoglycemic and analgesic effects.

AB - Type 2 diabetes mellitus (T2DM) is considered the "pandemic of the 21st century." It is a complex multifactorial disease associated with chronic hyperglycemia, causing further complications that result in disability and early mortality. Due to the fact that the main focus of T2DM therapy is to reduce the patient's blood sugar levels, avoiding drug-induced hypoglycemia is important. Free fatty acid receptor 1 (FFAR1) agonists are considered promising hypoglycemic agents without the risk of hypoglycemia. In the future, FFAR1 agonists may expand the range of safer hypoglycemic agents with a mechanism of action not currently used in T2DM therapy. In this study, the hypoglycemic effect of a novel and potent FFAR1 agonist based on benzyloxyphenylpropanoic acid's core containing an aminobornyl fragment was investigated in a long-term experiment on C57BL/6 Ay/a (Agouti Yellow) mice. The results demonstrated a reduction in insulin resistance, attributed to the hepatoprotective effect of the compound. Additionally, the analgesic effect of the compound was evaluated in experimental pain models. It appeared that the compound exhibited a moderate analgesic effect at high doses. Furthermore, the FFAR1-mediated mechanism of action was confirmed through experiments with an FFAR1 antagonist coadministration, which suppressed both hypoglycemic and analgesic effects.

KW - Animals

KW - Hypoglycemic Agents/pharmacology

KW - Receptors, G-Protein-Coupled/agonists

KW - Mice

KW - Analgesics/pharmacology

KW - Mice, Inbred C57BL

KW - Male

KW - Structure-Activity Relationship

KW - Dose-Response Relationship, Drug

KW - Blood Glucose/drug effects

KW - Molecular Structure

KW - Pain/drug therapy

KW - Phenylpropionates/pharmacology

KW - Diabetes Mellitus, Type 2/drug therapy

KW - Insulin Resistance

KW - Disease Models, Animal

U2 - 10.1002/ardp.70152

DO - 10.1002/ardp.70152

M3 - Article

C2 - 41262055

VL - 358

JO - Archiv der Pharmazie

JF - Archiv der Pharmazie

SN - 0365-6233

IS - 11

M1 - e70152

ER -