Estradiol dimers as a new class of steroid sulfatase reversible inhibitors.
A series of estradiol dimers was synthesized or selected from compounds available in our laboratory and tested for inhibition against steroid sulfatase. Dimers linked by their C17 position, compounds 7 and 8, showed inhibitory potency similar (56% and 54% at 1 microM) to that of our best previously reported reversible inhibitor EM-690 (62% at 1 microM). Docking experiment seems to indicate that C17-C17 dimers bind in a similar way to EM-690 whereas C16-O3 and C16-C16 dimers bind in an upside-down position.
Fournier
Diane
D
Medicinal Chemistry Division, Oncology and Molecular Endocrinology Laboratory, CHUQ-CHUL Research Center and Université Laval, Que., Canada G1V 4G2.
Poirier
Donald
D
D000970:Antineoplastic Agents / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019281:Dimerization; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry; D004958:Estradiol / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D015233:Models, Statistical; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy; D013256:Steroids / Q000737:chemistry; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013256:Steroids; D004958:Estradiol; D043266:Steryl-Sulfatase