Design and synthesis of polyhydroxy steroids as selective inhibitors against AKR1B10 and molecular docking

作者：Chen, Wenli; Chen, Xinying; Zhou, Shujia; Zhang, Hong; Wang, Ling; Xu, Jun; Hu, Xiaopeng; Yin, Wei; Yan, Guangmei; Zhang, Jingxia^*

来源：Steroids, 2016, 110: 1-8.

DOI：10.1016/j.steroids.2016.03.004

• Synthesis
• Polyhydroxy steroids
• AKR1B10
• Selective inhibitor
• Anti-cancer

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 mu M 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.

• 出版日期2016-6
• 单位中山大学