Androstane-3β-O-sulfonate 및 -sulfamate 유도체 합성과 steroid sulfatase 저해효과

Synthesis and Steroid Sulfatase Inhibitory Effect of Androstane-3β-O-sulfonate and -sulfamate Derivatives

The development of potent steroid sulfatase inhibitors is an important new therapeutic strategy for the treatment of postmenopausal women with breast cancer. In postmenopausal breast cancer, the desulfation of dehydroepiandrostene sulfate (DHEAS) by steroid sulfatase (STS) that takes place in peripheral tissues becomes as an important step in estrogen production. Androstane-3β-O-mesylsulfonate, -3β-O-tosylsulfonate, and -3β-O-sulfamate derivatives with substituents at positions 5 and 6 were synthesized using DHEA as the parent structure and STS inhibitory activity was measured at 3 μM in human Jeg-3 cells. 6β-Chloro-5α-hydroxyandrostane-3β-O-sulfamate (13) was found to be the most active compound with STS inhibition 71%.