20-O-beta-glucopyranosyl camptothecin from mostuea brunonis: A potential camptothecin pro-drug with improved solubility.
Bioassay-guided fractionation of the organic extracts of whole plants of Mostuea brunonis (Loganiaceae), using the National Cancer Institute's (NCI) human tumor-based in vitro antitumor screen, led to the isolation and identification of camptothecin 20-O-beta-D-glucoside (1) and three moderately cytotoxic alkaloids, the known deoxypumiloside (2) and strictosamide (3), and the new 2'-O-acetylstrictosamide (4), from the cytotoxic alkaloid fractions. While the previously unknown 20-O-beta-D-glucopyranosyl camptothecin exhibited greater solubility in alcohol, DMSO-H(2)O and H(2)O than camptothecin, it was essentially inactive in the NCI's in vitro 60-cell line primary antitumor screen. However, it could be vulnerable to de-glucosidation in vivo, and may, therefore, merit additional evaluation as a potential prodrug of camptothecin that could be more readily formulated than the parent agent.
Dai
J R
JR
Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick Cancer Research & Development Center, Building 1052, Room 121 Frederick, MD.
Hallock
Y F
YF
Cardellina II
J H
JH
Boyd
M R
MR
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D010944:Plants / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry / Q000302:isolation & purification*; D014407:Tumor Cells, Cultured
C400585:20-O-glucopyranosyl camptothecin; D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D002166:Camptothecin