Efficient construction of novel D-ring modified steroidal dienamides and their cytotoxic activities.

Abstract: Two series of steroidal dienamides 4a–q and 5a–f were designed, synthesized and evaluated for cytotoxic activities against five human cancer cell lines (MGC-803, EC109, PC-3, SMMC-7721 and MCF-7). The protocol developed efficiently achieved the construction of carbon–carbon double bond and selective conversion of nitrile group into carboxamide in one-pot procedure. Besides, compounds 4a–q and 5a–f showed moderate to excellent cytotoxic activities with the IC50 values ranging from 0.1 to 40 μM and most of them were more potent than 5-fluorouracil. Particularly, four compounds 4d, 4e, 4q and 5a showed excellent selectivity against MGC-803 with the IC50 values less than 1 μM. Flow cytometry analysis demonstrated that compound 4c caused the cellular early apoptosis and cell cycle arrest in G2/M phase in a concentration-independent manner. [Copyright &y& Elsevier]