Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes |
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| Authors: | Massimo Genovese Concetta Imperatore Marcello Casertano Anna Aiello Francesco Balestri Lucia Piazza Marialuisa Menna Antonella Del Corso Paolo Paoli |
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| Institution: | 1.Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy;2.Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy; (C.I.); (M.C.); (A.A.);3.Biochemistry Unit, Department of Biology, University of Pisa, Via S. Zeno, 51, 56123 Pisa, Italy; (F.B.); (L.P.) |
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| 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. |
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| Keywords: | marine natural products metabolic diseases type 2 diabetes mellitus protein tyrosine phosphatase 1B aldose reductase multitarget drugs |
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