ESTRONE SULFONATES AS INHIBITORS OF ESTRONE SULFATASE

In our continuing quest to design efficient inhibitors of estrone sulf atase activity and to assess the recognition of estrone sulfate surrog ates by estrone sulfatase, we synthesized and evaluated several sulfon ate derivatives of 5,6,7,8-tetrahydronaphth-2-ol and estrone. 5,6,7, 8 -Tetrahydronaphth-2-methanesulfonate (II), and 5,6,7, 8-tetra-hydronap hth-2-(p-toluene)sulfonate (12) were found not to inhibit estrone sulf atase activity; estrone-3-methane-sulfonate (5), estrone-3-ethanesulfo nate (6), estrone-3-butanesulfonate (7), and estrone-3-[(+)10-camphor] sulfonate (8) all weakly inhibited estrone sulfatase, and the best inh ibitor from this class of compounds, was estrone-3-(p-toluene)sulfonat e (9). At 10 mu M, it inhibited estrone sulfatase activity by 91%. The se results emphasize some of the requirements needed for high-affinity binding to the enzyme. (C) 1997 by Elsevier Science Inc.