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

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2021 Oct 22

PMID 34677434

Citations 7

Authors

Massimo Genovese

Concetta Imperatore

Marcello Casertano

Anna Aiello

Francesco Balestri

Lucia Piazza

Marialuisa Menna

Antonella Del Corso

Paolo Paoli

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Marine-Derived Phosphoeleganin and Its Semisynthetic Derivative Decrease IL6 Levels and Improve Insulin Signaling in Human Hepatocellular Carcinoma Cells.

Agognon A, Casertano M, Vito A, Orso S, Cabaro S, Mormone F Int J Mol Sci. 2024; 25(11).

PMID: 38892230 PMC: 11173279. DOI: 10.3390/ijms25116039.

Searching for Novel Sources of Hydrogen Sulfide Donors: Chemical Profiling of Extract and Evaluation of the Anti-Inflammatory Effects.

Casertano M, Esposito E, Bello I, Indolfi C, Putra M, Di Cesare Mannelli L Mar Drugs. 2023; 21(12).

PMID: 38132963 PMC: 10744941. DOI: 10.3390/md21120641.

Natural Bioactive Compounds from Marine Invertebrates That Modulate Key Targets Implicated in the Onset of Type 2 Diabetes Mellitus (T2DM) and Its Complications.

Casertano M, Vito A, Aiello A, Imperatore C, Menna M Pharmaceutics. 2023; 15(9).

PMID: 37765290 PMC: 10538088. DOI: 10.3390/pharmaceutics15092321.

Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge .

Casertano M, Genovese M, Santi A, Pranzini E, Balestri F, Piazza L Pharmaceutics. 2023; 15(2).

PMID: 36839851 PMC: 9964544. DOI: 10.3390/pharmaceutics15020528.

Molecular and Biological Investigation of Isolated Marine Fungal Metabolites as Anticancer Agents: A Multi-Target Approach.

Bogari H, Elhady S, Darwish K, Refaey M, Mohamed R, Abdelhameed R Metabolites. 2023; 13(2).

PMID: 36837781 PMC: 9964656. DOI: 10.3390/metabo13020162.

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