کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1376925 | 981967 | 2008 | 4 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Phosphoramidate derivatives of hydroxysteroids as inhibitors of prostate-specific membrane antigen Phosphoramidate derivatives of hydroxysteroids as inhibitors of prostate-specific membrane antigen](/preview/png/1376925.png)
Prostate-specific membrane antigen (PSMA) is a membrane-bound cell surface peptidase which is over-expressed in prostate cancer cells. The enzymatic activities of PSMA are understood but the role of the enzyme in prostate cancer remains conjectural. We previously confirmed the existence of a hydrophobic binding site remote from the enzyme’s catalytic center. To explore the specificity and accommodation of this binding site, we prepared a series of six glutamate-containing phosphoramidate derivatives of various hydroxysteroids (1a–1f). The inhibitory potencies of the individual compounds of the series were comparable to a simple phenylalkyl analog (8), and in all cases IC50 values were sub-micromolar. Molecular docking was used to develop a binding model for these inhibitors and to understand their relative inhibitory potencies against PSMA.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 1, 1 January 2008, Pages 281–284