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Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes

An in-depth study on the inhibitory mechanism on protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR) enzymes, including analysis of the insulin signalling pathway, of phosphoeleganin, a marine-derived phosphorylated polyketide, was achieved. Phosphoeleganin was demonstrated to inhibit...

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Autores principales: Genovese, Massimo, Imperatore, Concetta, Casertano, Marcello, Aiello, Anna, Balestri, Francesco, Piazza, Lucia, Menna, Marialuisa, Del Corso, Antonella, Paoli, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540617/
https://www.ncbi.nlm.nih.gov/pubmed/34677434
http://dx.doi.org/10.3390/md19100535
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author Genovese, Massimo
Imperatore, Concetta
Casertano, Marcello
Aiello, Anna
Balestri, Francesco
Piazza, Lucia
Menna, Marialuisa
Del Corso, Antonella
Paoli, Paolo
author_facet Genovese, Massimo
Imperatore, Concetta
Casertano, Marcello
Aiello, Anna
Balestri, Francesco
Piazza, Lucia
Menna, Marialuisa
Del Corso, Antonella
Paoli, Paolo
author_sort Genovese, Massimo
collection PubMed
description An in-depth study on the inhibitory mechanism on protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR) enzymes, including analysis of the insulin signalling pathway, of phosphoeleganin, a marine-derived phosphorylated polyketide, was achieved. Phosphoeleganin was demonstrated to inhibit both enzymes, acting respectively as a pure non-competitive inhibitor of PTP1B and a mixed-type inhibitor of AR. In addition, in silico docking analyses to evaluate the interaction mode of phosphoeleganin with both enzymes were performed. Interestingly, this study showed that phosphoeleganin is the first example of a dual inhibitor polyketide extracted from a marine invertebrate, and it could be used as a versatile scaffold structure for the synthesis of new designed multiple ligands.
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spelling pubmed-85406172021-10-24 Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes Genovese, Massimo Imperatore, Concetta Casertano, Marcello Aiello, Anna Balestri, Francesco Piazza, Lucia Menna, Marialuisa Del Corso, Antonella Paoli, Paolo Mar Drugs Article An in-depth study on the inhibitory mechanism on protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR) enzymes, including analysis of the insulin signalling pathway, of phosphoeleganin, a marine-derived phosphorylated polyketide, was achieved. Phosphoeleganin was demonstrated to inhibit both enzymes, acting respectively as a pure non-competitive inhibitor of PTP1B and a mixed-type inhibitor of AR. In addition, in silico docking analyses to evaluate the interaction mode of phosphoeleganin with both enzymes were performed. Interestingly, this study showed that phosphoeleganin is the first example of a dual inhibitor polyketide extracted from a marine invertebrate, and it could be used as a versatile scaffold structure for the synthesis of new designed multiple ligands. MDPI 2021-09-24 /pmc/articles/PMC8540617/ /pubmed/34677434 http://dx.doi.org/10.3390/md19100535 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Genovese, Massimo
Imperatore, Concetta
Casertano, Marcello
Aiello, Anna
Balestri, Francesco
Piazza, Lucia
Menna, Marialuisa
Del Corso, Antonella
Paoli, Paolo
Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes
title Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes
title_full Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes
title_fullStr Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes
title_full_unstemmed Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes
title_short Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes
title_sort dual targeting of ptp1b and aldose reductase with marine drug phosphoeleganin: a promising strategy for treatment of type 2 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540617/
https://www.ncbi.nlm.nih.gov/pubmed/34677434
http://dx.doi.org/10.3390/md19100535
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