59(P-35) 放線菌由来の新規ICAM-1/LFA-1依存性細胞接着阻害物質、Adxanthromycinに関する研究(ポスター発表の部)

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Intercellular adhesion molecule-1 (ICAM-1: CD54) and lymphocyte function antigen-1 (LFA-1: CD11a/CD18) are cell surface adhesion molecules that interact with one another to promote a number of cellular interactions, including antigen-specific T lymphocyte stimulation and leukocyte adhesion to endothelium followed by emigration into site of inflammation. Therefore, a new inhibitor of ICAM-1 and LFA-1 system could be a potential therapeutic drug for inflammatory and immunological disease. A search for inhibitors of ICAM-1/LFA-1 mediated cell adhesion molecule from microbial metabolites was carried out using two methodologies: a homotypic JY cell aggregation assay and a cell adhesion assay using soluble ICAM-1 and LFA-1 positive SKW-3 T cell leukemia cells. During the screening program, we have isolated two novel inhibitors, designated as adxanthromycins A (1) and B (2), from the cultured broth of Streptomyces sp. NA-148. The chemical structures of both inhibitors were determined to be dimeric anthrone peroxides containing one or two moieties of α-D-galactose by various NMR spectral analyses [PFG (pulsed field gradient)-DQFCOSY, PFG-HMQC, PFG-HMBC, NOE difference and NOESY experiments] and chemical degradation studies. Compounds 1 and 2 inhibited homotypic aggregation of JY cells from the concentration of 1.5μg/ml in a dose depended manner, and a complete inhibition was observed at the concentration of 6.25μg/ml. Compounds 1 and 2 also inhibited SKW-3 adhesion to soluble ICAM-1 in a dose-dependent manner with an IC^<50> of 18.8μg/ml and 25.0μg/ml, respectively.
天然有機化合物討論会の論文
2000-10-01

59(P-35) 放線菌由来の新規ICAM-1/LFA-1依存性細胞接着阻害物質、Adxanthromycinに関する研究(ポスター発表の部)

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