Isolation of the protein tyrosine phosphatase 1B inhibitory metabolite from the marine-derived fungus Cosmospora sp. SF-5060

Changon Seo; Jae Hak Sohn; Hyuncheol Oh; Bo Yeon Kim; Jong Seog Ahn

doi:10.1016/j.bmcl.2009.09.025

Isolation of the protein tyrosine phosphatase 1B inhibitory metabolite from the marine-derived fungus Cosmospora sp. SF-5060

Bioorg Med Chem Lett. 2009 Nov 1;19(21):6095-7. doi: 10.1016/j.bmcl.2009.09.025. Epub 2009 Sep 12.

Authors

Changon Seo¹, Jae Hak Sohn, Hyuncheol Oh, Bo Yeon Kim, Jong Seog Ahn

Affiliation

¹ College of Medical and Life Sciences, Silla University, San 1-1 Gwaebeop-dong, Sasang-gu, Busan 617-736, Republic of Korea.

PMID: 19782562
DOI: 10.1016/j.bmcl.2009.09.025

Abstract

In the course of bioassay-guided study on the EtOAc extract of a culture broth of the marine-derived fungus Cosmospora sp. SF-5060, aquastatin A (1) was isolated as a protein tyrosine phosphatase 1B (PTP1B) inhibitory component produced by the fungus. The compound was isolated by various chromatographic methods, and the structure was determined mainly by analysis of NMR spectroscopic data. Compound 1 exhibited potent inhibitory activity against PTP1B with IC(50) value of 0.19muM, and the kinetic analyses of PTP1B inhibition by compound 1 suggested that the compound is inhibiting PTP1B activity in a competitive manner. Aquastatin A (1) also showed modest but selective inhibitory activity toward PTP1B over other protein tyrosine phosphatases, such as TCPTP, SHP-2, LAR, and CD45. In addition, the result of hydrolyzing aquastatin A (1) suggested that the dihydroxypentadecyl benzoic acid moiety in the molecule is responsible for the inhibitory activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzoates / chemistry*
Benzoates / isolation & purification
Benzoates / pharmacology
Binding, Competitive
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology
Fungi / chemistry*
Galactosides / chemistry*
Galactosides / isolation & purification
Galactosides / pharmacology
Kinetics
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 2 / antagonists & inhibitors
Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism
Salicylates

Substances

Benzoates
Enzyme Inhibitors
Galactosides
Salicylates
aquastatin A
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatase, Non-Receptor Type 2