Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1396186 | European Journal of Medicinal Chemistry | 2011 | 11 Pages |
Steroid sulfatase (STS) controls the levels of 3-hydroxysteroids available from circulating steroid sulfates in several normal and malignant tissues. This and the known involvement of active estrogens and androgens in diseases such as breast and prostate cancers thus make STS an interesting therapeutic target. Here we describe the chemical synthesis and characterization of an extended series of 17α-derivatives of estradiol (E2) using different strategies. A variant of the samarium-Barbier reaction with stoichiometric samarium metal and catalytic Kagan reagent formation was used for introducing low reactive benzyl substrates in position 17 of estrone (E1) whereas heterocyclic substrates were metalated and reacted with either the carbonyl or the 17-oxirane of E1. In vitro evaluation of the inhibitory potency of the new compounds against STS identified new inhibitors and allowed a more complete structure–activity relationship study of this family of 17α-derivatives of E2.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Molten salt route to Bi3NbO7 nanoparticles. ► The enzyme steroid sulfatase is an interesting therapeutic target. ► Introducing a side-chain at position 17α of estradiol can inhibit steroid sulfatase. ► The pi–pi interaction between a 17α-group and phenylalanine residues seems unlikely. ► The use of Kagan reagent increases reactivity towards hindered steroidal ketones.