title: Madindoline, a novel inhibitor of IL-6 activity from Streptomyces sp. K93-0711. I. Taxonomy, fermentation, isolation and biological activities.
abstract: Selective growth inhibition against IL-6-dependent cells was detected in fermentation extracts of a microbial strain, K93-0711, which was characterized as Streptomyces species. Active metabolite, termed madindoline A and B, were isolated, and the structure was determined to be 3a-hydroxy-indoline with diketocyclopentene at the N position. Madindoline A and B displayed dose-dependent inhibition of MH60 cells, an IL-6-dependent cell line, in presence of 0.1 U/ml IL-6. The IC50 for madindoline A and B against this cell line was 8 microM and 30 microM, respectively. These compounds did not inhibit the growth of cell lines which are not IL-6 dependent and the growth inhibition of the MH60 cell line was reversed by addition of excess, 0.4 U/ml, of IL-6 to the culture media. These compounds did not show any antimicrobial activity at a concentration of 1,000 micrograms/ml.
authors.affiliation: Kitasato Institute, Kitasato University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: Y P
authors.initials: YP
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Takamatsu
authors.forename: A
authors.initials: A
authors.lastname: Enomoto
authors.forename: M
authors.initials: M
authors.lastname: Shinose
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Komiyama
authors.forename: S
authors.initials: S
authors.lastname: Omura
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000302:isolation & purification* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005285:Fermentation; D006801:Humans; D007211:Indoles / Q000302:isolation & purification* / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000188:drug therapy; D013302:Streptomyces; D000093242:Interleukin-6 Inhibitors
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D000093242:Interleukin-6 Inhibitors; C103158:madindoline A