Cytotoxic activities of hypocretenolides from Leontodon hispidus

The hypocretenolides are a small group of sesquiterpene lactones with an un usual ring structure and are constituents of several species from the tribe Lactuceae of the family Asteraceae. In the present communication we report on the cytotoxic effects of three hypocretenolides (1-3) from Leontodon hi spidus on: (a) eight solid-tumor cell lines (A431, HEPS, MCF7, OVCAR3, SK28 , SK37, SW872, ZR75-1), tested by a H-3-thymidine incorporation assay; (b) two different leukemia cell lines (GTB, HL60), measured by a MTT assay; and (c) CD34(+) bone-marrow cells, assessed by scoring the number of colonies derived from primitive and late erythroid progenitors (BFU-E and CFU-E) as well as from granulocytic/macrophagic progenitor cells (CFU-GM). The aglyco n 14-hydroxyhypocretenolide (1) exhibited pronounced activities, although i ts beta-D-glucoside (2) showed no activity, even at the highest concentrati on tested (2 mu M). 14-Hydroxyhypocretenolide-beta-D-glucoside-4',14"-hydro xyhypocretenoate (3), the ester of the glucoside esterified with the open-c hain form of the aglycon, was the most potently cytotoxic substance and pro ved to be even more active than the positive-control substance helenalin.