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Isatin derivatives as a new class of aldose reductase inhibitors with antioxidant activity

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Abstract

In this work, isatin was employed as the scaffold to design aldose reductase inhibitors with antioxidant activity. Most of the isatin derivatives were proved to be excellent in the inhibition of aldose reductase (ALR2) with IC50 values at submicromolar level, and (E)-2-(5-(4-methoxystyryl)-2,3-dioxoindolin-1-yl) acetic acid (9g) was identified as the most effective with an IC50 value of 0.015 μM. Moreover, compounds 9a–h with styryl side chains at the C5 position of isatin showed potent antioxidant activity. Particularly, the phenolic compound 9h demonstrated similar antioxidant activity with the well-known antioxidant Trolox. Structure-activity relationship and molecular docking studies showed that the acetic acid group at N1 and C5 p-hydroxystyryl side chain were the key structures to increase the aldose reductase inhibitory activity and antioxidant activity.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant no. 21572021).

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Zhongguancun South Street, Beijing, China

    Wenchao Liu, Huan Chen, Xiaonan Zhang, Xin Zhang, Long Xu, Yanqi Lei, Changjin Zhu & Bing Ma

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  1. Wenchao Liu
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  2. Huan Chen
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  3. Xiaonan Zhang
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  4. Xin Zhang
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Correspondence to Bing Ma.

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Liu, W., Chen, H., Zhang, X. et al. Isatin derivatives as a new class of aldose reductase inhibitors with antioxidant activity. Med Chem Res 30, 1588–1602 (2021). https://doi.org/10.1007/s00044-021-02751-4

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