LAUSR

HIGHLIGHTS9,19‐cyclolanostane derivatives starting from cycloastragenol were synthesized.Five analogs were selected to be screened for their anti‐inflammatory properties.The compounds inhibited NF&kgr;B activation.They were shown to be promising anti‐inflammatory agents.The compounds are noteworthy candidates for prostate cancer chemoprevention. ABSTRACT Chronic inflammation is associated to 25% of cancer cases according to epidemiological data. Therefore, inhibition of inflammation‐induced carcinogenesis can be an efficient therapeutic approach for cancer chemoprevention in drug development studies. It is also determined that anti‐inflammatory drugs reduce cancer incidence. Cell culture‐based in vitro screening methods are used as a fast and efficient method to investigate the biological activities of the biomolecules. In addition, saponins are molecules that are isolated from natural sources and are known to have potential for tumor inhibition. Studies on the preparation of analogues of cycloartane‐type sapogenols (9,19‐cyclolanostanes) have so far been limited. Therefore we have decided to direct our efforts toward the exploration of new anti‐tumor agents prepared from cycloastragenol and its production artifact astragenol. The semi‐synthetic derivatives were prepared mainly by oxidation, condensation, alkylation, acylation, and elimination reactions. After preliminary studies, five sapogenol analogues, two of which were new compounds (2 and 3), were selected and screened for their inhibitory activity on cell viability and NF&kgr;B signaling pathway activity in LNCaP prostate cancer cells. We found that the astragenol derivatives 1 and 2 as well as cycloastragenol derivatives 3, 4, and 5 exhibited strong inhibitory activity on NF&kgr;B signaling leading the repression of NF&kgr;B transcriptional activation and suppressed cell proliferation. The results suggested that these molecules might have significant potential for chemoprevention of prostate carcinogenesis induced by inflammatory NF&kgr;B signaling pathway.