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Inhibition of protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase by xanthones from Cratoxylum cochinchinense, and their kinetic characterization.

Authors :
Li ZP
Song YH
Uddin Z
Wang Y
Park KH
Source :
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2018 Feb 01; Vol. 26 (3), pp. 737-746. Date of Electronic Publication: 2017 Dec 26.
Publication Year :
2018

Abstract

Cratoxylum cochinchinense displayed significant inhibition against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase, both of which are key target enzymes to attenuate diabetes and obesity. The compounds responsible for both enzymes inhibition were identified as twelve xanthones (1-12) among which compounds 1 and 2 were found to be new ones. All of them simultaneously inhibited PTP1B with IC <subscript>50</subscript> s of (2.4-52.5 µM), and α-glucosidase with IC <subscript>50</subscript> values of (1.7-72.7 µM), respectively. Cratoxanthone A (3) and γ-mangostin (7) were estimated to be most active inhibitors against both PTP1B (IC <subscript>50</subscript>  = 2.4 µM for 3, 2.8 µM for 7) and α-glucosidase (IC <subscript>50</subscript>  = 4.8 µM for 3, 1.7 µM for 7). In kinetic studies, all isolated xanthones emerged to be mixed inhibitors of α-glucosidase, whereas they behaved as competitive inhibitors of PTP1B. In time dependent experiments, compound 3 showed isomerization inhibitory behavior with following kinetic parameters: K <subscript>i</subscript> <superscript>app</superscript>  = 2.4 µM; k <subscript>5</subscript>  = 0.05001 µM <superscript>-1</superscript>  S <superscript>-1</superscript> and k <subscript>6</subscript>  = 0.02076 µM <superscript>-1</superscript>  S <superscript>-1</superscript> .<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3391
Volume :
26
Issue :
3
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry
Publication Type :
Academic Journal
Accession number :
29306546
Full Text :
https://doi.org/10.1016/j.bmc.2017.12.043