Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
Braz. J. Pharm. Sci. (Online)
; 56: e00222, 2020. tab, graf
Article
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LILACS-Express
| LILACS
| ID: biblio-1089183
Responsable en Bibliothèque :
BR1.1
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.
Texte intégral:
1
Indice:
LILACS
Type d'étude:
Prognostic_studies
langue:
En
Texte intégral:
Braz. J. Pharm. Sci. (Online)
Thème du journal:
Farmacologia
/
Teraputica
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Toxicologia
Année:
2020
Type:
Article
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Project document