Pladienolides, new substances from culture of Streptomyces platensis Mer-11107. I. Taxonomy, fermentation, isolation and screening.
Seven new macrolides having a 12-membered ring, which we termed pladienolides, were isolated from the fermentation broth of Streptomyces platensis Mer-11107. Six of the seven pladienolides inhibited hypoxia-induced reporter gene expression controlled by human VEGF promoter with IC50 values of 0.0018-2.89 microM. They also demonstrated growth-inhibitory activity against U251 human glioma cells in vitro. Pladienolides are highly potent inhibitors of both hypoxia signals and cancer cell proliferation, and thus may be useful as antitumor agents.
Sakai
Takashi
T
Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3, Tokodai, Tsukuba, Ibaraki 300-2635, Japan. t3-sakai@hhc.eisai.co.jp
Sameshima
Tomohiro
T
Matsufuji
Motoko
M
Kawamura
Naoto
N
Dobashi
Kazuyuki
K
Mizui
Yoshiharu
Y
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000235:genetics; D000970:Antineoplastic Agents / Q000145:classification / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics; D018942:Macrolides / Q000145:classification / Q000302:isolation & purification* / Q000494:pharmacology; D013302:Streptomyces; D014407:Tumor Cells, Cultured / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
D000970:Antineoplastic Agents; D007527:Isoenzymes; D018942:Macrolides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C055791:germ-cell AP isoenzyme; D000469:Alkaline Phosphatase