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

• 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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