Discovery of inhibitors of protein tyrosine phosphatase 1B contained in a natural products library from Mexican medicinal plants and fungi using a combination of enzymatic and in silico methods

Bibliographic Details
Title: Discovery of inhibitors of protein tyrosine phosphatase 1B contained in a natural products library from Mexican medicinal plants and fungi using a combination of enzymatic and in silico methods
Authors: Miriam Díaz-Rojas, Martin González-Andrade, Rodrigo Aguayo-Ortiz, Rogelio Rodríguez-Sotres, Araceli Pérez-Vásquez, Abraham Madariaga-Mazón, Rachel Mata
Source: Frontiers in Pharmacology, Vol 14 (2023)
Publisher Information: Frontiers Media S.A., 2023.
Publication Year: 2023
Collection: LCC:Therapeutics. Pharmacology
Subject Terms: PTP1B, chemical space, scaffold hops, canophyllol, E/Z vermelhotin, Therapeutics. Pharmacology, RM1-950
More Details: This work aimed to discover protein tyrosine phosphatase 1B (PTP1B) inhibitors from a small molecule library of natural products (NPs) derived from selected Mexican medicinal plants and fungi to find new hits for developing antidiabetic drugs. The products showing similar IC50 values to ursolic acid (UA) (positive control, IC50 = 26.5) were considered hits. These compounds were canophyllol (1), 5-O-(β-D-glucopyranosyl)-7-methoxy-3′,4′-dihydroxy-4-phenylcoumarin (2), 3,4-dimethoxy-2,5-phenanthrenediol (3), masticadienonic acid (4), 4′,5,6-trihydroxy-3′,7-dimethoxyflavone (5), E/Z vermelhotin (6), tajixanthone hydrate (7), quercetin-3-O-(6″-benzoyl)-β-D-galactoside (8), lichexanthone (9), melianodiol (10), and confusarin (11). According to the double-reciprocal plots, 1 was a non-competitive inhibitor, 3 a mixed-type, and 6 competitive. The chemical space analysis of the hits (IC50 < 100 μM) and compounds possessing activity (IC50 in the range of 100–1,000 μM) with the BIOFACQUIM library indicated that the active molecules are chemically diverse, covering most of the known Mexican NPs’ chemical space. Finally, a structure–activity similarity (SAS) map was built using the Tanimoto similarity index and PTP1B absolute inhibitory activity, which allows the identification of seven scaffold hops, namely, compounds 3, 5, 6, 7, 8, 9, and 11. Canophyllol (1), on the other hand, is a true analog of UA since it is an SAR continuous zone of the SAS map.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1663-9812
Relation: https://www.frontiersin.org/articles/10.3389/fphar.2023.1281045/full; https://doaj.org/toc/1663-9812
DOI: 10.3389/fphar.2023.1281045
Access URL: https://doaj.org/article/05e6978ed0304e5581f30093b1d3dda1
Accession Number: edsdoj.05e6978ed0304e5581f30093b1d3dda1
Database: Directory of Open Access Journals
More Details
ISSN:16639812
DOI:10.3389/fphar.2023.1281045
Published in:Frontiers in Pharmacology
Language:English