[摘要]：Narciclasine (1)(I) is a plant growth regulator that has been previously demonstrated to be proapoptotic to cancer cells at high concns. (? mM). Data generated in the present study show that narciclasine displays potent antitumor effects in apoptosis-resistant as well as in apoptosis-sensitive cancer cells by impairing the organization of the actin cytoskeleton in cancer cells at concns. that are not cytotoxic (IC50 values of 30-90 nM). The current study further revealed that any chem. modification to the narciclasine backbone generally led to compds. of variable stability, weaker activity, or even the complete loss of antiproliferative effects in vitro. However, one hemisynthetic deriv. of narciclasine, compd. 7k(II), demonstrated by both the i.v. and oral routes higher in vivo antitumor activity in human orthotopic glioma models in mice when compared to narciclasine at nontoxic doses. Narciclasine and compd. 7k may therefore be of potential use to combat brain tumors.
