Stephacidin A and B: two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cells.
Two novel antitumor alkaloids, Stephacidin A and B, were isolated from the solid fermentation of Aspergillus ochraceus WC76466. Both alkaloids exhibit in vitro cytotoxicity against a number of human tumor cell lines; however, stephacidin B demonstrated more potent and selective antitumor activities, especially against prostate testeosterone-dependent LNCaP cells with IC50 value of 60 nM. The structures of stephacidin A and B were established on the basis of the NMR data and X-ray crystallography. With 15 rings and 9 chiral centers, stephacidin B represents one of the most structurally complex and novel alkaloids occurring in nature.
Qian-Cutrone
Jingfang
J
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
Huang
Stella
S
Shu
Yue-Zhong
YZ
Vyas
Dolatrai
D
Fairchild
Craig
C
Menendez
Ana
A
Krampitz
Kimberly
K
Dalterio
Richard
R
Klohr
Steven E
SE
Gao
Qi
Q
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001235:Aspergillus ochraceus / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D026121:Indole Alkaloids; D007211:Indoles / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D019906:Nuclear Magnetic Resonance, Biomolecular; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013739:Testosterone / Q000502:physiology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D026121:Indole Alkaloids; D007211:Indoles; C470895:stephacidin A; C470894:stephacidin B; D013739:Testosterone