Isolation of a novel protein tyrosine phosphatase inhibitor, 2-methyl-fervenulone, and its precursors from Streptomyces.
High-throughput screening identified an extract from Streptomyces sp. IM 2096 with inhibitory activity toward several protein tyrosine phosphatases (PTPs). Four 1,2,4-triazine compounds 2096A-D (1-4) were isolated from this extract and their structures elucidated by interpretation of spectroscopic data and confirmed by degradation and synthesis. The novel glycocyamidine derivatives 1 and 2 are diastereomers and may interconvert. Both are inactive in the PTP inhibition assay. Compounds 1 and 2 are unstable and partially decompose to 3 and glycocyamidine (5) at room temperature. Compound 3, known as MSD-92 or 2-methyl-fervenulone, is a broad-specificity PTP inhibitor with comparable potency to vanadate. The imidazo[4, 5-e]-1,2,4-triazine (4), inactive in the PTP-inhibition assay, may be a degradation product of 3.
Wang
H
H
Medicinal and Combinatorial Chemistry Laboratory, Cell Regulation Laboratory, Lead Discovery Group, Microbial Collection and Screening Laboratory, Singapore.
Lim
K L
KL
Yeo
S L
SL
Xu
X
X
Sim
M M
MM
Ting
A E
AE
Wang
Y
Y
Yee
S
S
Tan
Y H
YH
Pallen
C J
CJ
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013057:Spectrum Analysis; D013302:Streptomyces / Q000201:enzymology*; D014227:Triazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
C421034:2-methyl-fervenulone; D004791:Enzyme Inhibitors; D014227:Triazines; D017027:Protein Tyrosine Phosphatases