Antitumor steroids: 2. Synthesis and biological activity of 11α-hydroxyestra-1,3,5,(10)-triene derivatives with bis-(2-chloroethyl)amino-containing substituents

Abstract

Antitumor steroids with a cytotoxic substituent attached to the steroid nucleus without participation of natural functional groups have been obtained by esterification of 3-acetates of 11a-hydroxy derivatives of estradiol and 17a-ethinylestradiol with para-[bis(2-chloroethyl)amino]phenylacetic acid using the carbodiimide method. Some substances of this series combine antitumor activity and antiestrogen properties. 523 0091-150X/07/4110-0523

Man-Made Cytotoxic Steroids: Exemplary Agents for Cancer Therapy

“…Compound 36 with free hydroxyl groups at C 3 and C 17 positions and an alkylating moiety substituted at position C 11 of 11α-hydroxyestra-1,3,5(10)-triene exhibited antitumor activity with total growth inhibition of 92% against mice bearing CA-755 breast adenocarcinoma and B-16 melanoma and also possessed antiestrogen properties. Overall the compounds with the alkylating group attached to C 3 of steroid are more active, which might be attributed to the less stable ester bond involving the C 3 phenolic −OH group, thus favoring an increased accumulation of nitrogen mustard moiety at the tumor site …”