Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome.
Mikhail E BlokhinSergey O KuranovMikhail Vladimirovich KhvostovVladislav V FomenkoOlga A LuzinaNatalia A ZhukovaCham ElhajjarTatiana G TolstikovaNariman F SalakhutdinovPublished in: Current issues in molecular biology (2023)
Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synthesized a number of potential agonists based on the pharmacophore fragment of glitazars with the inclusion of mono- or diterpenic moiety in the molecular structure. The study of their pharmacological activity in mice with obesity and type 2 diabetes mellitus (C57Bl/6 Ay ) revealed one substance that was capable of reducing the triglyceride levels in the liver and adipose tissue of mice by enhancing their catabolism and expressing a hypoglycemic effect connected with the sensitization of mice tissue to insulin. It has also been shown to have no toxic effects on the liver.
Keyphrases
- metabolic syndrome
- high fat diet induced
- insulin resistance
- adipose tissue
- type diabetes
- glycemic control
- molecular docking
- high fat diet
- blood glucose
- uric acid
- cardiovascular risk factors
- fatty acid
- wild type
- skeletal muscle
- molecular dynamics
- weight loss
- physical activity
- cardiovascular disease
- smoking cessation
- body mass index
- blood pressure
- risk assessment
- single cell