Steroid Sulfatase Inhibitors Based on Phosphate and Thiophosphate Flavone Analogs |
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| Authors: | Witold Kozak Mateusz Daśko Maciej Masłyk Konrad Kubiński Janusz Rachon Sebastian Demkowicz |
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| Affiliation: | 1. Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Gdansk, Poland;2. Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences, The John Paul II Catholic University of Lublin, Konstantynów 1i, Lublin, Poland |
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| 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. Drug Dev Res 76 : 450–462, 2015. © 2015 Wiley Periodicals, Inc. |
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| Keywords: | steroid sulfatase molecular modeling STS inhibitors breast cancer flavones |
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