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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Bibliographic Details
Published in:Marine drugs 2021-09, Vol.19 (10), p.535
Main Authors: Genovese, Massimo, Imperatore, Concetta, Casertano, Marcello, Aiello, Anna, Balestri, Francesco, Piazza, Lucia, Menna, Marialuisa, Del Corso, Antonella, Paoli, Paolo
Format: Article
Language:English
Subjects:
Aldehyde reductase
Aldehyde Reductase - metabolism
aldose reductase
Animals
Aquatic Organisms
Chronic illnesses
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - drug therapy
Disease
Drugs
Enzymes
Glucose
Hep G2 Cells - drug effects
Humans
Hyperglycemia
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - pharmacology
Hypoglycemic Agents - therapeutic use
Inhibitors
Insulin
Insulin resistance
Ligands
Marine invertebrates
marine natural products
Mediterranean Sea
metabolic diseases
Metabolism
Molecular Docking Simulation
multitarget drugs
Obesity
Oxidative stress
Phosphatase
Polyketides - chemistry
Polyketides - pharmacology
Polyketides - therapeutic use
protein tyrosine phosphatase 1B
Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism
Protein-tyrosine-phosphatase
Reductases
Signal Transduction
type 2 diabetes mellitus
Tyrosine
Urochordata
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Summary: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.
ISSN:1660-3397
1660-3397
DOI:10.3390/md19100535