α-Glucosidase Inhibitors Based on Oleanolic Acid for the Treatment of Immunometabolic Disorders

Using oleanolic acid as a starting compound, a series of new oleanane-type triterpenic derivatives were synthesized via O-acylation (with nicotinic, isonicotinic, and methoxycinnamic acid acyl chlorides), N-amidation (with cyclic- or polyamines), the Mannich reaction (with secondary cyclic amines),...

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Bibliographic Details
Published in:Applied sciences 2023-08, Vol.13 (16), p.9269
Main Authors: Petrova, Anastasiya V, Babkov, Denis A, Khusnutdinova, Elmira F, Baikova, Irina P, Kazakova, Oxana B, Sokolova, Elena V, Spasov, Alexander A
Format: Article
Language:English
Subjects:
Acylation
Antidiabetics
Chromatography
Dextrose
Diabetes
Enzymes
Glucose
Hydrolases
Hyperglycemia
indole
Mannich reaction
Medical research
Medicine, Experimental
oleanolic acid
Polyamines
triterpenoids
Type 2 diabetes
α-glucosidase inhibiting activity
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Summary:Using oleanolic acid as a starting compound, a series of new oleanane-type triterpenic derivatives were synthesized via O-acylation (with nicotinic, isonicotinic, and methoxycinnamic acid acyl chlorides), N-amidation (with cyclic- or polyamines), the Mannich reaction (with secondary cyclic amines), and Claisen–Schmidt condensation (with aromatic aldehydes), and their potencies as treatments for immunometabolic disorders were investigated. The compounds were evaluated against α-glucosidase and PTP1B enzymes and LPS-stimulated murine macrophages. It was found that the target compounds are highly effective α-glucosidase inhibitors but lack activity against PTP1B. A leading compound, N-methylpiperazine methylated 2,3-indolo-oleanolic propargyl amide 15, is also a micromolar inhibitor of NO synthesis in LPS-stimulated macrophages and suppresses oxidative bursts in neutrophils with similar efficiency. These results, in addition to its ability to stimulate glucose uptake in rat fibroblasts and improve maltose tolerance in rats, allow us to consider compound 15 a promising prototype drug for the treatment of immunometabolic defects in type 2 diabetes.
ISSN:2076-3417
2076-3417
DOI:10.3390/app13169269