α-Glucosidase Inhibitors Based on Oleanolic Acid for the Treatment of Immunometabolic Disorders
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Published:2023-08-15
Issue:16
Volume:13
Page:9269
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ISSN:2076-3417
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Container-title:Applied Sciences
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language:en
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Short-container-title:Applied Sciences
Author:
Petrova Anastasiya V.1ORCID, Babkov Denis A.2ORCID, Khusnutdinova Elmira F.1ORCID, Baikova Irina P.1, Kazakova Oxana B.1ORCID, Sokolova Elena V.2, Spasov Alexander A.2ORCID
Affiliation:
1. Ufa Institute of Chemistry, Ufa Federal Research Centre, Russian Academy of Science, 71 Pr., Oktyabrya Ufa 450054, Russia 2. Scientific Center for Innovative Drugs, Volgograd State Medical University, 39, Novorossiyskaya St., Volgograd 400087, Russia
Abstract
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.
Subject
Fluid Flow and Transfer Processes,Computer Science Applications,Process Chemistry and Technology,General Engineering,Instrumentation,General Materials Science
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