Discovery and optimization of new benzofuran derivatives against p53-independent malignant cancer cells through inhibition of HIF-1 pathway
| Autor: | Jia-Lin Wang, Jinlian Wei, Ying-Rui Yang, Qidong You, Xiao-fei Mo, Zhenwei Yuan, Chao Zhang, Haopeng Sun, Yi-Yue Xie |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Cell cycle checkpoint
Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Biology Pharmacology 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship 0302 clinical medicine Cell Line Tumor Neoplasms Drug Discovery medicine Structure–activity relationship Humans Benzofuran Molecular Biology Benzofurans Cell Proliferation Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Cell growth Drug discovery Organic Chemistry Cancer Cell Cycle Checkpoints medicine.disease HCT116 Cells 0104 chemical sciences chemistry Apoptosis 030220 oncology & carcinogenesis Cancer cell MCF-7 Cells Molecular Medicine Hypoxia-Inducible Factor 1 Drug Screening Assays Antitumor Tumor Suppressor Protein p53 |
| Zdroj: | Bioorganicmedicinal chemistry letters. 26(11) |
| ISSN: | 1464-3405 |
| Popis: | p53-independent malignant cancer is still severe health problem of human beings. HIF-1 pathway is believed to play an important role in the survival and developing progress of such cancers. In the present study, with the aim to inhibit the proliferation of p53-independent malignant cells, we disclose the optimization of 6a, the starting compound which is discovered in the screening of in-house compound collection. The structure-activity relationship (SAR) is summarized. The most potent derivative 8d, inhibits the proliferation of both p53-null and p53-mutated cells through inhibition of HIF-1 pathway. Our findings here provide a new chemotype in designing potent anticancer agent especially against those p53-independent malignant tumors. |
| Databáze: | OpenAIRE |
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