ABSTRACT
Over the past three decades, a number of steroid-alkylating agent conjugates have been synthesized and tested for antitumor potential. Estramustine is a conjugate of estradiol and nor-nitrogen mustard linked by a carbamate ester. The feature that distinguishes estramustine from other similar conjugates is the N-C=O motif (Fig. 1). The carbamate is especially resistant to enzymatic cleavage. An agent such as prednimustine (a prednisolone ester of chlorambucil) has an ester linkage, which is readily hydrolyzed by serum esterases. The presence of the carbamate group in estramustine creates a substrate with a biological half-life in humans that is greater than 16 h (1 ). This stabilization by the carbamate group has produced a drug with an unpredicted and unexpected mechanism of action.
