A One-Pot Synthesis and Biological Activity of Ageladine A and Analogues
| Autor: | Mélina Blairvacq, Wendy L. Loa-Kum-Cheung, Laurent Meijer, Peter Karuso, Sudhir R. Shengule, Christopher R. Parish, Yoichi Nakao |
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| Rok vydání: | 2011 |
| Předmět: |
Natural product
Neovascularization Pathologic Matrix metalloproteinase inhibitor Kinase Stereochemistry Antineoplastic Agents Biological activity Matrix Metalloproteinase Inhibitors Matrix metalloproteinase Inhibitory Concentration 50 chemistry.chemical_compound Biochemistry chemistry Cell culture Cell Line Tumor Drug Discovery Humans Molecular Medicine Pyrroles Drug Screening Assays Antitumor Kinase activity Cytotoxicity Protein Kinase Inhibitors Protein Kinases |
| Zdroj: | Journal of Medicinal Chemistry. 54:2492-2503 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm200039m |
| Popis: | A one-pot synthesis of ageladine A and analogues is reported. The key Pictet-Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition to develop the first structure-activity relationship of ageladine A analogues. One compound, which showed significant kinase activity but little MMP inhibitory activity, was found to be highly active in an antiangiogenic screen, suggesting that the angiogenic activity of ageladine A is not associated with MMP inhibition but rather kinase inhibitory activity. Cytotoxicity was excluded as a mode of action by the assay of ageladine A and an analogue against 60 human cell lines. |
| Databáze: | OpenAIRE |
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