کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2027605 | 1542698 | 2016 | 8 صفحه PDF | دانلود رایگان |
• Five pairs analogues of polyhydroxy steroids were designed, synthesized and structure identified.
• Novel inhibitors for AKR1B10 were developed.
• The brand new compound6 shows the high selective inhibitory activity for AKR1B10 against AKR1B1.
AKR1B10 is a member of the human aldo–keto reductase superfamily which is highly expressed in several types of cancers, and has been regarded as a promising cancer therapeutic target. In this paper, a series of polyhydroxy steroids were designed and synthesized to selectively inhibit AKR1B10 activity. The most selective compound, novel compound 6, has an IC50 of 0.83 ± 0.07 μM and a selectivity of more than 120-fold for AKR1B10/AKR1B1. Structure–activity relation analyses indicate that hydroxyl at C-19 can significantly improve the selective inhibition of AKR1B10. The binding mode of AKR1B10 and its inhibitors were studied.
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Journal: Steroids - Volume 110, June 2016, Pages 1–8