title: Synthesis and biological evaluation of N-acylated tyramine sulfamates containing C-F bonds as steroid sulfatase inhibitors.
abstract: Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un-sulfated forms and promotes the growth of various hormone-dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid-sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N-acylated tyramines that contain C-F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4-(2-perfluoroundecanoylaminoethyl)-phenyl sulfamate, 5r, demonstrated the greatest inhibitory effect, with an IC50value of 2.18 μm (IC50value of 2.13 μm for coumarin-7-O-sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Daśko
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Rachon
authors.affiliation: Department of Molecular Biology, Faculty of Biotechnology and Environmental Sciences, The John Paul II Catholic University of Lublin, Lublin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Masłyk
authors.affiliation: Department of Molecular Biology, Faculty of Biotechnology and Environmental Sciences, The John Paul II Catholic University of Lublin, Lublin, Poland.
authors.forename: Konrad
authors.initials: K
authors.lastname: Kubiński
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland.
authors.forename: Sebastian
authors.identifier: 0000-0002-4252-4297
authors.initials: S
authors.lastname: Demkowicz
mesh_terms: D000215:Acylation; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D005461:Fluorine / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D009584:Nitrogen / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D014439:Tyramine / Q000737:chemistry*
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D013451:Sulfonic Acids; C100462:coumarin 7-O-sulfamate; D005461:Fluorine; D002244:Carbon; C005741:sulfamic acid; D043266:Steryl-Sulfatase; D009584:Nitrogen; D014439:Tyramine
keywords: STS inhibitors; breast cancer; steroid sulfatase; sulfamates; tyramine