title: Phosphate and thiophosphate biphenyl analogs as steroid sulfatase inhibitors.
abstract: In the present work, we report convenient methods for the synthesis and biological evaluation of phosphate and thiophosphate biphenyl derivatives exhibiting steroid sulfatase (STS) activity. The described synthesis is based on straightforward preparation of biphenyl-4-ol and 4'-hydroxy-biphenyl-4-carboxylic acid ethyl ester modified with various phosphate or thiophosphate moieties. The inhibitory effects of these compounds were tested on STS isolated from human placenta and led to two compounds of interest, 5a and 5d with IC50 values of 28.0 and 22.1 µM, respectively and that had interesting new binding modes in the STS active site.
authors.affiliation: Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Demkowicz
authors.forename: Witold
authors.initials: W
authors.lastname: Kozak
authors.forename: Mateusz
authors.initials: M
authors.lastname: Daśko
authors.forename: Maciej
authors.initials: M
authors.lastname: Masłyk
authors.forename: Konrad
authors.initials: K
authors.lastname: Kubiński
authors.forename: Janusz
authors.initials: J
authors.lastname: Rachon
mesh_terms: D001665:Binding Sites; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D062105:Molecular Docking Simulation; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; C584039:STS protein, human; D043266:Steryl-Sulfatase
keywords: STS inhibitors; biphenyls; breast cancer; steroid sulfatase