Kozak Witold, Daśko Mateusz, Masłyk Maciej, Kubiński Konrad, Rachon Janusz, Demkowicz Sebastian
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences, The John Paul II Catholic University of Lublin, Konstantynów 1i, 20-708, Lublin, Poland.
Drug Dev Res. 2015 Dec;76(8):450-62. doi: 10.1002/ddr.21281. Epub 2015 Sep 28.
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.
