Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite.
A potent immunosuppressive activity was found in the culture broth of the fungus Isaria sinclairii (ATCC 24400). The metabolite, ISP-I ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2- hydroxymethyl-14-oxoeicos-6-enoic acid, myriocin = thermozymocidin) suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction, but had no effect on the growth of human tumor cell lines. It also suppressed the appearance of plaque-forming cells in response to sheep red blood cells and the generation of allo-reactive cytotoxic T lymphocytes in mice after intraperitoneal or oral administration. The metabolite was 10- to 100-fold more potent than cyclosporin A as an immunosuppressive agent of the immune response in vitro and in vivo, and appears to be a candidate for clinical application as a powerful immunosuppressant.
Fujita
T
T
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Inoue
K
K
Yamamoto
S
S
Ikumoto
T
T
Sasaki
S
S
Toyama
R
R
Chiba
K
K
Hoshino
Y
Y
Okumoto
T
T
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D016572:Cyclosporine / Q000276:immunology / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D005285:Fermentation; D005658:Fungi / Q000378:metabolism*; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
D000935:Antifungal Agents; D005229:Fatty Acids, Monounsaturated; D016572:Cyclosporine; C001996:thermozymocidin