硫酸酯酶
类固醇
芳基
生物化学
组合化学
对接(动物)
药物化学
基质(水族馆)
色酮
作者
Mateusz Daśko,Maciej Masłyk,Konrad Kubiński,Justyna Aszyk,Janusz Rachon,Sebastian Demkowicz
出处
期刊:MedChemComm
[The Royal Society of Chemistry]
日期:2016-06-16
卷期号:7 (6): 1146-1150
被引量:6
摘要
In the present work, we report convenient methods for the synthesis and biological evaluation of N-phosphorylated derivatives of 3-(4-aminophenyl)-coumarin-7-O-sulfamate as potential steroid sulfatase (STS) inhibitors. Their binding modes were modeled using docking techniques. The inhibitory effects of the synthesized compounds were tested on STS isolated from human placenta. All of the newly synthesised coumarin derivatives were powerful inhibitors of STS with IC50 values ranging between 0.19 and 0.78 μM. In particular, we found that 3-[4-(diphenoxy-phosphorylamino)-phenyl]-coumarin-7-O-sulfamate 10e and 3-[4-(dibenzyloxy-phosphorylamino)-phenyl]-coumarin-7-O-sulfamate 10f produced the highest inhibitory effects, with IC50 values of 0.19 and 0.24 μM, respectively (IC50 values of 1.38 μM for coumarin-7-O-sulfamate 2 and 1.03 μM for coumate 3 used as reference). The structure–activity relationships of the synthesized coumarin derivatives toward the STS enzyme were discussed.
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