Isolation of the protein tyrosine phosphatase 1B inhibitory metabolite from the marine-derived fungus Cosmospora sp. SF-5060.
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.
College of Medical and Life Sciences, Silla University, San 1-1 Gwaebeop-dong, Sasang-gu, Busan 617-736, Republic of Korea.
Changon
C
Seo
Jae Hak
JH
Sohn
Hyuncheol
H
Oh
Bo Yeon
BY
Kim
Jong Seog
JS
Ahn
D001565:Benzoates / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D005658:Fungi / Q000737:chemistry*; D005697:Galactosides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D007700:Kinetics; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012459:Salicylates
D001565:Benzoates; D004791:Enzyme Inhibitors; D005697:Galactosides; D012459:Salicylates; C085031:aquastatin A; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2