Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
Document title: Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
Journal: Brazilian Journal of Pharmaceutical Sciences
Database: PERIÓDICA
System number: 000451491
ISSN: 1984-8250
Authors: 1
1
2
2
2
Institutions: 1Zhejiang Ocean University, DongHai Science and Technology College, Zhejiang, Zhoushan. China
2Zhejiang Ocean University, Food and Pharmacy College, Zhejiang, Zhoushan. China
Year:
Volumen: 56
Country: Brasil
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English 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
Disciplines: Química
Keyword: Química farmacéutica,
Bioquímica,
Dioxoindolina-N-fenilacetamida,
Cinética enzimática,
Inhibidores enzimáticos,
Fosfatasas
Keyword: Medicinal chemistry,
Biochemistry,
Dioxoindolin-N-phenylacetamide,
Enzymatic kinetics,
Phosphatases
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