title: Estrone sulfonates as inhibitors of estrone sulfatase.
abstract: In our continuing quest to design efficient inhibitors of estrone sulfatase activity and to assess the recognition of estrone sulfate surrogates by estrone sulfatase, we synthesized and evaluated several sulfonate derivatives of 5,6,7,8-tetrahydronaphth-2-ol and estrone. 5,6,7,8-Tetrahydronaphth-2-methanesulfonate (11), and 5,6,7,8-tetrahydronaphth-2-(p-toluene)sulfonate (12) were found not to inhibit estrone sulfatase activity; estrone-3-methane-sulfonate (5), estrone-3-ethanesulfonate (6), estrone-3-butanesulfonate (7), and estrone-3-[(+)10-camphor]sulfonate (8) all weakly inhibited estrone sulfatase, and the best inhibitor, from this class of compounds, was estrone-3-(p-toluene)sulfonate (9). At 10 microM, it inhibited estrone sulfatase activity by 91%. These results emphasize some of the requirements needed for high-affinity binding to the enzyme.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Pharmacology, University of Bath, UK.
authors.forename: N M
authors.initials: NM
authors.lastname: Howarth
authors.forename: A
authors.initials: A
authors.lastname: Purohit
authors.forename: M J
authors.initials: MJ
authors.lastname: Reed
authors.forename: B V
authors.initials: BV
authors.lastname: Potter
mesh_terms: D002855:Chromatography, Thin Layer; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004970:Estrone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009284:Naphthols / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013429:Sulfatases / Q000037:antagonists & inhibitors*; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D009284:Naphthols; D013451:Sulfonic Acids; C088768:estrone-3-O-sulfamate; D004970:Estrone; D013429:Sulfatases; C020121:estrone sulfatase; C043496:5,6,7,8-tetrahydro-2-naphthol