Discovery of steroidal lactam conjugates of POPAM-NH with potent anticancer activity.

Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we aimed to develop steroidal prodrugs of the novel nitrogen mustard POPAM-NH. POPAM-NH is a melphalan analogue that was coupled with three different steroidal lactams. The new conjugates were preclinically tested for anticancer activity against nine human and one rodent cancer experimental models, and . All the steroidal alkylators showed high antitumor activity, and , in the experimental systems tested. Moreover, these hybrid compounds showed by far superior anticancer activity compared with the alkylating agents, melphalan and POPAM-NH.