title: Synthesis of bicoumarin thiophosphate derivatives as steroid sulfatase inhibitors.
abstract: Based on the frameworks of 7-hydroxy-2,3-dihydro-1H-cyclopenta[c]chromen-4-one, 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one and 3-hydroxy-8,9,10,11-tetrahydro-7H-cyclohepta[c]chromen-6-one, a series of bicoumarin thiophosphate analogs have been synthesized and biologically evaluated. Additionally, their binding modes have been modeled using docking techniques. The inhibitory properties of the synthesized compounds were tested against the STS isolated from human placenta. Most of the new STS inhibitors possessed good activities against STS. In particular, we found that the bis-(6-oxo-7,8,9,10-tetrahydro-6H-benzo[c]chromen-3-yl) hydrogenthiophosphate (10b) produced the largest inhibitory effect, with an IC50 value of 860 nM (an IC50 value of 1 μM for the 665-COUMATE used as a reference). The structure-activity relationships of the synthesized bicoumarin thiophosphate derivatives toward the STS enzyme have been discussed previously.
authors.affiliation: Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland. Electronic address: sebdemko@pg.gda.pl.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Demkowicz
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: Bartłomiej
authors.initials: B
authors.lastname: Gielniewski
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
mesh_terms: D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D063086:Organothiophosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; D063086:Organothiophosphates; C000607740:bis(6-oxo-7,8,9,10-tetrahydro-6H-benzo(c)chromen-3-yl) hydrogen thiophosphate; D043266:Steryl-Sulfatase
keywords: Bicoumarin thiophosphates; Breast cancer; Molecular docking; STS inhibitors; Steroid sulfatase