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-β-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-β-D-glucopyranosyl camptothecin exhibited greater solubility in alcohol, DMSO-H2O and H2O 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.
antitumor activity, Mostuea brunonis, cytotoxic alkaloid, camptothecin glycoside
NCBI PubMed ID: 10543908Publication DOI: 10.1021/np990100mJournal NLM ID: 7906882Publisher: American Society of Pharmacognosy
Correspondence:
Institutions: 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, Maryland 21702-1201, USA
Methods: 13C NMR, 1H NMR, IR, HPLC, UV, optical rotation measurement, cytotoxicity assay, HMBC, HMQC, DEPT, COSY, HR-FAB-MS, LR-CI-MS
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