Identification and optimization of novel 6-acylamino-2-aminoquinolines as potent Hsp90 C-terminal inhibitors
Autor: | An-ping Guo, Xiao-fei Mo, Xiao-Li Xu, Jia-cheng Xu, Fen Jiang, Qi-Dong You, Hui-Jie Wang |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Antineoplastic Agents Apoptosis Pharmacology Mice Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Drug Discovery medicine Animals Humans Structure–activity relationship HSP90 Heat-Shock Proteins Aminoquinolines skin and connective tissue diseases Novobiocin Cell Proliferation Mice Inbred BALB C Virtual screening Dose-Response Relationship Drug Molecular Structure Cell growth Organic Chemistry Neoplasms Experimental General Medicine Molecular Docking Simulation 030104 developmental biology chemistry SKBR3 030220 oncology & carcinogenesis Female Drug Screening Assays Antitumor Lead compound Derivative (chemistry) medicine.drug |
Zdroj: | European Journal of Medicinal Chemistry. 141:1-14 |
ISSN: | 0223-5234 |
Popis: | In order to discover novel Hsp90 inhibitors targeting the C-terminal ATP binding pocket, a novobiocin derivative based ROCS model was constructed for virtual screening. Compound 13 was identified as the lead compound and then systematical structure activity relationship (SAR) study was conducted. These efforts led to compound 69, which exhibited potent anti-proliferative activities against MCF7 and SKBr3 breast cancer cell lines. In 4T1 mice breast cancer models, 69 exhibited potent tumor growth inhibition and anti-metastasis effect. Compound 69 as a potent antitumor agent targeting the Hsp90 C-terminal is worthy of further pre-clinical study. |
Databáze: | OpenAIRE |
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