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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