20-O-beta-glucopyranosyl camptothecin from Mostuea brunonis: A potential camptothecin pre-drug with improved solubility

Bioassay-guided fractionation of the organic extracts of whole plants of Mo stuea brunonis (Loganiaceae), using the National Cancer Institute's (NCI) h uman tumor-based in vitro antitumor screen, led to the isolation and identi fication of camptothecin 20-O-beta-D-glucoside (1) and three moderately cyt otoxic 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 exhi bited greater solubility in alcohol, DMSO-H2O and H2O than camptothecin, it was essentially inactive in the NCI's in vitro 60-cell line primary antitu mor screen. However, it could be vulnerable to de-glucosidation in vivo, an d may, therefore, merit additional evaluation as a potential prodrug of cam ptothecin that could be more readily formulated than the parent agent.