Characterization of B-5354c, a New Sphingosine Kinase Inhibitor, Produced by a Marine Bacterium

• Published in: Journal of antibiotics 2000/08/25, Vol.53(8), pp.759-764
• Main Authors: KONO, KEITA, TANAKA, MASAHIRO, OGITA, TAKESHI, KOHAMA, TAKAFUMI
• Format: Article
• Language: English
• Subjects: 4-Aminobenzoic Acid - chemistry; 4-Aminobenzoic Acid - pharmacology; Animals; Antibiotics (antibacterial agents, antifungal agents); Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Applied microbiology; Bacteria; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - enzymology; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; General pharmacology; Gram-Negative Bacteria - metabolism; Humans; Inhibitory Concentration 50; Kinetics; Medical sciences; Microbiology; para-Aminobenzoates; Pharmacology. Drug treatments; Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors; Physicochemical properties. Structure-activity relationships; Rats; sphingosine; Sphingosine kinase; Structure-Activity Relationship; Substrate Specificity
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.53.759

B-5354c is a new inhibitor of sphingosine kinase from a novel marine bacterium, SANK 71896. Kinetic study revealed that B-5354c inhibits sphingosine kinase with a Ki value of 12μM. The inhibition is noncompetitive with respect to sphingosine. The compound also inhibits sphingosine-1-phosphate formation in human platelets. Experiments using synthetic derivatives of B-5354c indicate that all the three functional groups, i.e., the long unsaturated aliphatic chain, 4-amino and 3-hydroxyl groups are necessary to inhibit sphingosine kinase.