Madindoline, a novel inhibitor of IL-6 activity from Streptomyces sp. K93-0711. I. Taxonomy, fermentation, isolation and biological activities.
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.
Hayashi
M
M
Kitasato Institute, Kitasato University, Tokyo, Japan.
Kim
Y P
YP
Takamatsu
S
S
Enomoto
A
A
Shinose
M
M
Takahashi
Y
Y
Tanaka
H
H
Komiyama
K
K
Omura
S
S
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
D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D000093242:Interleukin-6 Inhibitors; C103158:madindoline A