20-O-beta-glucopyranosyl camptothecin from mostuea brunonis: A potential camptothecin pro-drug with improved solubility.

Abstract

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.

• Authors: J R Dai, Y F Hallock, J H Cardellina II, M R Boyd
• Journal: Journal of natural products (J Nat Prod) Vol. 62 Issue 10 Pg. 1427-9 (Oct 1999) ISSN: 0163-3864 [Print] United States
• PMID: 10543908 (Publication Type: Journal Article)

Chemical References

• 20-O-glucopyranosyl camptothecin
• Antineoplastic Agents, Phytogenic
• Prodrugs
• Camptothecin

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification)
• Camptothecin (analogs & derivatives, chemistry, isolation & purification, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Magnetic Resonance Spectroscopy
• Mass Spectrometry (methods)
• Molecular Structure
• Plants (chemistry)
• Prodrugs (chemistry, isolation & purification)
• Tumor Cells, Cultured