Synthesis and sulfatase inhibitory activities of (E)- and (Z)-4-hydroxytamoxifen sulfamates

We report the development of (E)- and (Z)-4-hydroxytamoxifen sulfamates as estrone sulfatase inhibitors, potential therapeutic agents for the treatment of breast cancer. Both compounds competitively inhibit estrone sulfatase isolated from rat liver with apparent Ki of 35.9 μM for (E)-4-hydroxytamoxifen sulfamate and an apparent Ki of > 500 μM for the (Z) isomer. Abstract We report the development of (E)-and (Z)-4-hydroxytamoxifen sulfamates as estrone sulfatase inhibitors, potential therapeutic agents for the treatment of breast cancer. Both compounds competitively inhibit rat liver estrone sulfatase, with an apparent Ki of 35.9 μM for (E)-4-hydroxytamoxifen sulfamate and an apparent Ki of > 500 μM for the (Z) isomer.