title: Steroid Sulfatase Inhibitors Based on Phosphate and Thiophosphate Flavone Analogs.
abstract: A series of phosphate and thiophosphate flavone derivatives were synthesized and biologically evaluated in vitro for inhibition of steroid sulfatase (STS) activity. The described synthesis includes the straightforward preparation of 7-hydroxy-2-phenyl-4H-chromen-4-one 3a, 2-(4-fluorophenyl)-7-hydroxy-4H-chromen-4-one 3b, 7-hydroxy-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one 3c, 7-hydroxy-2-(p-tolyl)-4H-chromen-4-one 3d modified with different phosphate or thiophosphate moieties. The inhibitory properties of the synthesized compounds were tested against human placenta STS. Some of the novel STS inhibitors had good activities against STS. In particular, the bis-(4-oxo-2-(p-tolyl)-4H-chromen-7-yl) hydrogenthiophosphate, 6i had the most potent inhibitory effect with an IC50 value of 3.25 µM as compared to an IC50 value of 8.50 µM for the 2-(4-trifluoromethylphenyl)-chromen-4-one-7-O-sulfamate used as a reference.
authors.affiliation: Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Kozak
authors.affiliation: Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Daśko
authors.affiliation: Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences, The John Paul II Catholic University of Lublin, Konstantynów 1i, 20-708, Lublin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Masłyk
authors.affiliation: Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences, The John Paul II Catholic University of Lublin, Konstantynów 1i, 20-708, Lublin, Poland.
authors.forename: Konrad
authors.initials: K
authors.lastname: Kubiński
authors.affiliation: Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Rachon
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
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D047309:Flavones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D010710:Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000302:isolation & purification
chemical_list: D004791:Enzyme Inhibitors; D047309:Flavones; D010710:Phosphates; C584039:STS protein, human; D043266:Steryl-Sulfatase; C035638:thiophosphoric acid
keywords: STS inhibitors; breast cancer; flavones; molecular modeling; steroid sulfatase