Synthesis and biological evaluation of novel thiadiazole amides as potent Cdc25B and PTP1B inhibitors
| Autor: | Yingjun Li, Yang Yu, Jia Li, Xin Shao, Li Sheng, Li-Xin Gao, Tongchuan Luo, Kun Jin |
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| Rok vydání: | 2014 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science Biochemistry Structure-Activity Relationship chemistry.chemical_compound Amide Thiadiazoles Drug Discovery Ic50 values Humans cdc25 Phosphatases Enzyme Inhibitors Molecular Biology IC50 Oleanolic acid Biological evaluation Protein Tyrosine Phosphatase Non-Receptor Type 1 chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Amides Kinetics Enzyme Molecular Medicine Selectivity hormones hormone substitutes and hormone antagonists Nuclear chemistry |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 24:4125-4128 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2014.07.055 |
| Popis: | A series of novel thiadiazole amide derivatives have been synthesized and evaluated for inhibitory activities against Cdc25B and PTP1B. Most of them showed inhibitory activities against Cdc25B (IC50=1.18-8.01 μg/mL) and PTP1B (IC50=0.85-8.75 μg/mL), respectively. Moreover, compounds 5b and 4l were most potent with IC50 values of 1.18 and 0.85 μg/mL for Cdc25B and PTP1B, respectively, compared with reference drugs Na3VO4 (IC50=0.93 μg/mL) and oleanolic acid (IC50=0.85 μg/mL). The results of selectivity experiments showed that the target compounds were selective inhibitors against PTP1B and Cdc25B. Enzyme kinetic experiments demonstrated that compound 5k was a specific inhibitor with the typical characteristics of a mixed inhibitor. |
| Databáze: | OpenAIRE |
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