Aim: 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-NH2. POPAM-NH2 is a melphalan analogue
that was coupled with three different steroidal lactams. Methodology:
The new conjugates were preclinically tested for anticancer activity
against nine human and one rodent cancer experimental models, in vitro
and in vivo. Results & conclusion: All the steroidal alkylators showed
high antitumor activity, in vitro and in vivo, in the experimental
systems tested. Moreover, these hybrid compounds showed by far superior
anticancer activity compared with the alkylating agents, melphalan and
POPAM-NH2.
[GRAPHICS]
