Synthesis of new steroidal quinolines with antitumor properties

The incorporation of the heterocycles into the steroid nucleus has been recognized as a useful strategy to develop new steroidal agents for disease treatment. Representative examples are abiraterone and galeterone, which are presently used in clinic for the treatment of advanced prostate cancers. Herein we have developed the first Al₂O₃/KF-promoted pfitzinger reactions for the synthesis of new steroidal quinolines. These new steroidal quinolines showed moderate to good antiproliferative activity against several human lung cancer cells. Of these compounds, compound 2f exhibited the best potency toward the tested three lung cancer cells with IC₅₀ values <10 μM. Mechanistic studies showed that compound 2f concentration-dependently inhibited colony formation, morphological changes, apoptosis, and migration of A549 cells. To conclude, compound 2f could be used as a hit compound for developing steroid-based anti-lung cancer agents.