PMID- 35337123
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220329
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 15
IP  - 3
DP  - 2022 Mar 8
TI  - Identifying Human PTP1B Enzyme Inhibitors from Marine Natural Products: 
      Perspectives for Developing of Novel Insulin-Mimetic Drugs.
LID - 10.3390/ph15030325 [doi]
LID - 325
AB  - Diabetes mellitus (DM) represents a complex and multifactorial disease that 
      causes metabolic disorders with acute and long-term serious complications. The 
      onset of DM, with over 90% of cases of diabetes classified as type 2, implies 
      several metabolic dysfunctions leading to consider DM a worldwide health problem. 
      In this frame, protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR) 
      are two emerging targets involved in the development of type 2 diabetes mellitus 
      (T2DM) and its chronic complications. Herein, we employed a marine-derived dual 
      type inhibitor of these enzymes, phosphoeleganin, as chemical starting point to 
      perform a fragment-based process in search for new inhibitors. Phosphoeleganin 
      was both disassembled by its oxidative cleavage and used as model structure for 
      the synthesis of a small library of functionalized derivatives as rationally 
      designed analogues. Pharmacological screening supported by in silico docking 
      analysis outlined the mechanism of action against PTP1B exerted by a 
      phosphorylated fragment and a synthetic simplified analogue, which represent the 
      most potent inhibitors in the library.
FAU - Casertano, Marcello
AU  - Casertano M
AUID- ORCID: 0000-0001-5037-712X
AD  - Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
FAU - Genovese, Massimo
AU  - Genovese M
AUID- ORCID: 0000-0002-3732-3124
AD  - Department of Experimental and Clinical Biomedical Sciences, University of 
      Florence, 50134 Florence, Italy.
FAU - Piazza, Lucia
AU  - Piazza L
AD  - Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy.
FAU - Balestri, Francesco
AU  - Balestri F
AD  - Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy.
FAU - Del Corso, Antonella
AU  - Del Corso A
AUID- ORCID: 0000-0003-3165-6128
AD  - Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy.
FAU - Vito, Alessio
AU  - Vito A
AD  - Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
FAU - Paoli, Paolo
AU  - Paoli P
AUID- ORCID: 0000-0001-6448-7266
AD  - Department of Experimental and Clinical Biomedical Sciences, University of 
      Florence, 50134 Florence, Italy.
FAU - Santi, Alice
AU  - Santi A
AD  - Department of Experimental and Clinical Biomedical Sciences, University of 
      Florence, 50134 Florence, Italy.
FAU - Imperatore, Concetta
AU  - Imperatore C
AUID- ORCID: 0000-0001-7377-0653
AD  - Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
FAU - Menna, Marialuisa
AU  - Menna M
AUID- ORCID: 0000-0002-4515-3014
AD  - Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
LA  - eng
GR  - B61G18000470007/Regione Campania/
GR  - Bando contributo alla ricerca anno 2021/Department of Pharmacy, University of 
      Naples Federico II/
GR  - Fondi di Ateneo 2021/University of Florence/
PT  - Journal Article
DEP - 20220308
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC8950868
OTO - NOTNLM
OT  - aldose reductase
OT  - insulin-mimetic drugs
OT  - marine natural products
OT  - marine-inspired chemical libraries
OT  - protein tyrosine phosphatase 1B
OT  - type 2 diabetes mellitus
COIS- The authors declare no conflict of interest.
EDAT- 2022/03/27 06:00
MHDA- 2022/03/27 06:01
PMCR- 2022/03/08
CRDT- 2022/03/26 01:08
PHST- 2022/01/21 00:00 [received]
PHST- 2022/03/04 00:00 [revised]
PHST- 2022/03/07 00:00 [accepted]
PHST- 2022/03/26 01:08 [entrez]
PHST- 2022/03/27 06:00 [pubmed]
PHST- 2022/03/27 06:01 [medline]
PHST- 2022/03/08 00:00 [pmc-release]
AID - ph15030325 [pii]
AID - pharmaceuticals-15-00325 [pii]
AID - 10.3390/ph15030325 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2022 Mar 8;15(3):325. doi: 10.3390/ph15030325.