ABSTRACT
The synthesis and biological activity of a series of 2-[(4-methylthiopyridin-2-yl)methylsulfinyl]benzimidazoles are described. These compounds have potent inhibitory effects against the protein tyrosine phosphatase activity of CD45. Enzymatic analysis with several phosphatases revealed that compound 5a had high specificity for CD45 compared with serine/threonine phosphatases (PP1, PP2A), tyrosine phosphatases (LAR, PTP1B and PTP-S2) and dual phosphatase (VHR).
Subject(s)
Benzimidazoles/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Protein Tyrosine Phosphatases/antagonists & inhibitors , Sulfoxides/chemical synthesis , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Leukocyte Common Antigens/metabolism , Protein Tyrosine Phosphatases/metabolism , Structure-Activity Relationship , Sulfoxides/chemistry , Sulfoxides/pharmacologyABSTRACT
Phosphatoquinones A and B were isolated from the cultured broth of Streptomyces sp. TA-0363 and their structures were elucidated by spectroscopic analyses. Phosphatoquinones A and B inhibited the protein tyrosine phosphatase activity prepared from human Ball-1 cells with IC50 of 28 microM and 2.9 microM, respectively.
Subject(s)
Enzyme Inhibitors/pharmacology , Protein Tyrosine Phosphatases/antagonists & inhibitors , Quinones/pharmacology , Streptomyces/metabolism , Cell Line , Enzyme Inhibitors/isolation & purification , Fermentation , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Quinones/isolation & purification , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, Ultraviolet , Streptomyces/chemistry , Streptomyces/classificationABSTRACT
A new platelet aggregation inhibitor, bassiatin, was isolated from the cultured broth of Beauveria bassiana which had been isolated from a soil sample collected in Yunnan province, China. The structure of bassiatin was determined to be (3S, 6R)-4-methyl-6-(1-methylethyl)-3-phenylmethyl-1, 4-perhydrooxazine-2,5-dione by NMR analysis, X-ray crystallographic analysis and chemical synthesis. Bassiatin inhibited ADP-induced aggregation of rabbit platelets with the IC50 being 1.9 x 10(-4) M.
Subject(s)
Mitosporic Fungi/metabolism , Morpholines/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Animals , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microscopy, Electron, Scanning , Mitosporic Fungi/ultrastructure , Molecular Structure , Morpholines/chemistry , Platelet Aggregation Inhibitors/chemistry , RabbitsABSTRACT
Two new platelet aggregation inhibitors, PI-200 and PI-201 were isolated from the fermentation broth of Streptomyces sp. A7498. PI-200 and PI-201 inhibited ADP-induced aggregation of rabbit platelets with an IC50 of 3.8 x 10(-4) M and 7.1 x 10(-4) M, respectively.
