Synthesis and Biological Evaluation of Fluorinated 3-Phenylcoumarin-7-O-Sulfamate Derivatives as Steroid Sulfatase Inhibitors.
In the present work, we report the initial results of our study on a series of 3-phenylcoumarin sulfamate-based compounds containing C-F bonds as novel inhibitors of steroid sulfatase. The new compounds are potent steroid sulfatase inhibitors, possessing more than 10 times higher inhibitory potency than coumarin-7-O-sulfamate. In the course of our investigation, compounds 2b and 2c demonstrated the highest inhibitory effect on the enzymatic steroid sulfatase assay; both had IC50 values of 0.27 μm (the IC50 value of coumarin-7-O-sulfamate is 3.5 μm, used as a reference).
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
Sebastian
S
Demkowicz
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
Mateusz
M
Daśko
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
Witold
W
Kozak
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
Katarzyna
K
Krawczyk
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
Dariusz
D
Witt
Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences, The John Paul II Catholic University of Lublin, Konstantynów 1i, 20-708, Lublin, Poland.
Maciej
M
Masłyk
Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences, The John Paul II Catholic University of Lublin, Konstantynów 1i, 20-708, Lublin, Poland.
Konrad
K
Kubiński
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
Janusz
J
Rachon
D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D030562:Databases, Protein; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D054879:Halogenation; D006801:Humans; D020128:Inhibitory Concentration 50; D011485:Protein Binding; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
D003374:Coumarins; D004791:Enzyme Inhibitors; D013449:Sulfonamides; C100462:coumarin 7-O-sulfamate; D043266:Steryl-Sulfatase
breast cancer; coumarin; steroid sulfatase; steroid sulfatase inhibitors; sulfamates