Discovery of Chromeno[4,3-c]pyrazol-4(2H)-one Containing Carbonyl or Oxime Derivatives as Potential, Selective Inhibitors PI3Kα
| Autor: | Hai-Liang Zhu, Baozhong Wang, Yan-Dong Liu, Shao Sha, Guo-Dong Ju, Liang Lu, Kai Wang, Yuan-Heng Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
biology Chemistry Drug discovery Stereochemistry Active site General Chemistry General Medicine Oxime In vitro 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Docking (molecular) 030220 oncology & carcinogenesis Drug Discovery biology.protein Molecule Structure–activity relationship IC50 |
| Zdroj: | CHEMICAL & PHARMACEUTICAL BULLETIN. 64:1576-1581 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.c16-00388 |
| Popis: | A series of novel chromeno[4,3-c]pyrazol-4(2H)-one containing carbonyl or oxime derivatives (4a-n, 5a-n) have been synthesized and evaluated their biological activities as phosphatidyl inositol 3-kinase (PI3K) inhibitors. Out of them, compound 5l showed the most potent antiproliferative activities against HCT-116 with IC50 of 0.10 µM in vitro, and exhibited the most potent activity for PI3Kα with the value of 0.012 µM. Docking simulation of 5l into PI3Kα active site were performed to determine the probable binding model, and it indicated that compound 5l could be optimized as a potential inhibitor of PI3Kα in the further study. |
| Databáze: | OpenAIRE |
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