Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors

Authors

  • Qing-Hao Jin Zhejiang Ocean University, DongHai Science and Technology College
  • Wen-Bo Chen Zhejiang Ocean University, DongHai Science and Technology College https://orcid.org/0000-0001-8812-9973
  • Ya-Nan Xia Zhejiang Ocean University, Food and Pharmacy College
  • Bing-Yu Liu Zhejiang Ocean University, Food and Pharmacy College
  • Li-Ping Guan Zhejiang Ocean University, Food and Pharmacy College

DOI:

https://doi.org/10.1590/s2175-97902019000400222

Keywords:

: Dioxoindolin-N-phenylacetamide, CDC25B, PTP1B, Phosphatase inhibitors, Enzyme kinetics

Abstract

A series of 2,3-dioxoindolin-N-phenylacetamide derivatives was evaluated for inhibitory activity against CDC25B and PTP1B enzymes. Most of the derivatives showed inhibitory activity against CDC25B (IC50 = 3.2–23.2 µg/mL) and PTP1B (IC50 = 2.9–21.4 µg/mL). Compound 2h showed the most inhibitory activity in vitro with IC50 values of 3.2 and 2.9 µg/mL against CDC25B and PTP1B, respectively, compared with the reference drugs Na3VO4 (IC50 = 2.7 µg/mL) and oleanolic acid (IC50 = 2.3 µg/mL). The results of selectivity experiments showed that the 2,3-dioxoindolin-N-phenylacetamide derivatives were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor. In cytotoxic activity assays compound 2h had potent activity against A549, HeLa, and HCT116 cell lines. In addition, compound 2h showed potent tumor inhibitory activity in a colo205 xenograft model in vivo.

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Published

2020-12-09

How to Cite

Jin, Q.-H. ., Chen, W.-B. ., Xia, Y.-N. ., Liu, B.-Y. ., & Guan, L.-P. . (2020). Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors. Brazilian Journal of Pharmaceutical Sciences, 56, e00222. https://doi.org/10.1590/s2175-97902019000400222

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