Chemical modification of PA-48153C, a novel immunosuppressant isolated from Streptomyces prunicolor PA-48153.
5beta-Methoxy (20), 14-methyl (24), 14,14-dibromo-15-nor (25), 8-O-acyl (26-45), 8-O-alkyl (46), 8-O-alkoxycarbonyl (47, 48), and 8-O-carbamoyl (49) derivatives of PA-48153C, a novel immunosuppressant isolated from fermentation products of Streptomyces prunicolor PA-48153, were prepared. These compounds were found to retain the inhibitory activity on the responses of both T and B cells to mitogens. Among them, the C-8 hexanoate 28 showed potent suppressive effects on mitogen responses with less cytotoxicity to EL4 cells and was selected for in vivo evaluation.
Yasui
K
K
Shionogi & Co., Ltd., Osaka, Japan.
Tamura
Y
Y
Nakatani
T
T
Horibe
I
I
Kawada
K
K
Koizumi
K
K
Suzuki
R
R
Ohtani
M
M
D000818:Animals; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011753:Pyrones / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D018629:Spectrometry, Mass, Secondary Ion; D013302:Streptomyces / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D011753:Pyrones; C088446:pironetin