Rational design, synthesis, and in vivo evaluation of the antileukemic activity of six new alkylating steroidal esters

The synthesis and the in vivo evaluation against leukemias P388 and L1210 of six new alkylating steroidal esters are described. The esteric derivatives incorporating the 17 beta-acetamido-B-lactamic steroidal skeleton exhibited increased antileukemic activity and lower toxicity, compared to the 17 beta-acetamido-7-keto analogs. Among the 17 beta-acetamido-B-lactamic steroidal esters, the most potent compound afforded four out of six cures in leukemia P388 and was measured to be almost non-toxic, producing significant low levels of toxicity. (C) 2008 Elsevier Ltd. All rights reserved.