Isolation and structure elucidation of a novel androgen antagonist, arabilin, produced by Streptomyces sp. MK756-CF1.
In the course of screening for a new type of androgen receptor (AR) antagonist, we isolated a novel compound, arabilin, with two structural isomers, spectinabilin and SNF4435C, produced by Streptomyces sp. MK756-CF1. Structure elucidation on the basis of the spectroscopic properties showed that arabilin is a novel polypropionate-derived metabolite with a p-nitrophenyl group and a substituted γ-pyrone ring. Arabilin competitively blocked the binding of androgen to the ligand-binding domain of AR in vitro. In addition, arabilin inhibited androgen-induced prostate-specific antigen mRNA expression in prostate cancer LNCaP cells.
Kawamura
Tatsuro
T
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Fujimaki
Takahiro
T
Hamanaka
Natsuki
N
Torii
Kentaro
K
Kobayashi
Hiroki
H
Takahashi
Yoshikazu
Y
Igarashi
Masayuki
M
Kinoshita
Naoko
N
Nishimura
Yoshio
Y
Tashiro
Etsu
E
Imoto
Masaya
M
D000726:Androgen Antagonists / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009574:Nitro Compounds / Q000302:isolation & purification; D017430:Prostate-Specific Antigen / Q000187:drug effects* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011485:Protein Binding; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013057:Spectrum Analysis / Q000379:methods; D013237:Stereoisomerism; D013302:Streptomyces / Q000378:metabolism*
D000726:Androgen Antagonists; D009574:Nitro Compounds; D011753:Pyrones; D012333:RNA, Messenger; C435067:SNF 4435C; C553367:arabilin; C508401:spectinabilin; D017430:Prostate-Specific Antigen