title: 2-phenylindole sulfamates: inhibitors of steroid sulfatase with antiproliferative activity in MCF-7 breast cancer cells.
abstract: A number of 2-phenylindole sulfamates with lipophilic side chains in 1- or 5-position of the indole were synthesized and evaluated as steroid sulfatase (estrone sulfatase) inhibitors. Most of the new sulfamates inhibited the enzymatic hydrolysis of estrone sulfate in MDA-MB 231 breast cancer cells with IC(50) values between 2 nM and 1 microM. A favorable position for a long side chain is the nitrogen of a carbamoyl group at C-5 of the indole when the phenyl ring carries the sulfamate function. These derivatives inhibit gene activation in estrogen receptor (ER)-positive MCF-7 breast cancer cells in submicromolar concentrations and reduce cell proliferation with IC(50) values of ca. 1 microM. All of the potent inhibitors were devoid of estrogenic activity and have the potential for in vivo application as steroid sulfatase inhibitors.
authors.affiliation: Institut für Pharmazie, Universität Regensburg, D-93040 Regensburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Walter
authors.forename: Renate
authors.initials: R
authors.lastname: Liebl
authors.forename: Erwin
authors.initials: E
authors.lastname: von Angerer
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D011960:Receptors, Estrogen / Q000378:metabolism; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology*; D015533:Transcriptional Activation
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011960:Receptors, Estrogen; D013451:Sulfonic Acids; D004970:Estrone; C005741:sulfamic acid; D043266:Steryl-Sulfatase; C017296:estrone sulfate