LAUSR

Phytoecdysteroids are herbal analogs of the arthropod molting hormone, and, also considering their various metabolic bioactivities exerted in mammals, they appear to play a complex ecological role in the chemical communication between the Kingdoms of Nature. In addition to this, our group has recently revealed the ability of less polar analogs of these compounds to effectively sensitize cancer cells of various origin to several different types of chemotherapeutic agents. In a most recent study, we found that fluorination of 20‐hydroxyecdysone 2,3;20,22‐diacetonide can increase the chemo‐sensitizing activity on a susceptible (i.e. not multidrug resistant) cancer cell line as compared to that of its parental compound. This effect was, however, also accompanied by a stronger functional inhibition of the ABCB1 efflux transporter (P‐glycoprotein). Our attention was then turned to studying related structure–activity relationships of the analogs of poststerone (1), considering that this compound is an in vivo metabolite of the abundant 20‐hydroxyecdysone (20E) and that the side chain (not present in Compound 1) could be suspected to have relatively little importance in the chemo‐sensitizing activity. Moreover, poststerone 2,3‐dioxolane derivatives including poststerone 2,3‐acetonide were found to retain the multi drug resistance (MDR)‐selectivity of their chemo‐sensitizing effect, while exerting no inhibition on P‐glycoprotein function. Accordingly, we attempted to prepare fluorinated derivatives of poststerone similarly as before, in order to obtain new ecdysteroids and to further elaborate the structure–activity relationships concerning the antitumor potential of these compounds.