Antineoplastic agents 500. Narcistatin.
An efficient procedure was found for synthetic conversion of the sparingly soluble anticancer isocarbostyril narciclasine (1), a component of various Narcissus species, to a cyclic phosphate designated narcistatin (3b). The reaction between narciclasine, tetrabutylammonium dihydrogen phosphate, and p-toluenesulfonic acid in pyridine afforded pyridinium narcistatin (3a) in reasonable yields. Transformation of narcistatin (3a) to, for example, the water-soluble prodrug sodium narcistatin (3d) was easily achieved by cation exchange chromatography. Narcistatin (3b) and 15 salt derivatives were evaluated against a panel of human cancer cell lines, and the range (0.1-0.01) of GI(50) values in micro g/mL was found to parallel that shown by the parent narciclasine.
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-2404, USA.
Melody
Noeleen
N
Simpson
Michael
M
Thompson
Michael
M
Herald
Delbert L
DL
Knight
John C
JC
D000470:Alkaloids / Q000737:chemistry*; D047151:Amaryllidaceae Alkaloids; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007941:Leukemia P388; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D031427:Narcissus / Q000737:chemistry*; D010755:Organophosphates / Q000138:chemical synthesis / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010617:Phenanthridines; D010946:Plants, Medicinal / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000470:Alkaloids; D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D006576:Heterocyclic Compounds, 4 or More Rings; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010617:Phenanthridines; D011355:Prodrugs; D000644:Quaternary Ammonium Compounds; C474550:narcistatin; C010753:narciclasine