Anticancer activity of koningic acid and semisynthetic derivatives
| Autor: | Nicolas J. Rahier, Mangesh Jiotode, Rahul R. Lavhale, François Sautel, Arun Balakrishnan, Abhijeet S. Kate, Shilpa Amit Verekar, Sunil K. Deshmukh, Yannick Aussagues, Prafull Ranadive, Pradipta Tokdar, Céline Robichon, Arnaud Samson, Bruno Gomes, Samuel Meignan, Christian Bailly, Nicolas Molinier, Christophe Long |
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| Rok vydání: | 2015 |
| Předmět: |
Lung Neoplasms
Clinical Biochemistry Mice Nude Pharmaceutical Science Epoxide Antineoplastic Agents Sesquiterpene lactone Biochemistry Inhibitory Concentration 50 Mice Structure-Activity Relationship chemistry.chemical_compound In vivo Cell Line Tumor Drug Discovery Animals Humans Cytotoxicity Molecular Biology Glyceraldehyde 3-phosphate dehydrogenase Trichoderma chemistry.chemical_classification biology Organic Chemistry Xenograft Model Antitumor Assays Semisynthesis Cell Hypoxia In vitro Tumor Burden chemistry Fermentation biology.protein Molecular Medicine Glycolysis Sesquiterpenes |
| Zdroj: | Bioorganic & Medicinal Chemistry. 23:3712-3721 |
| ISSN: | 0968-0896 |
| Popis: | A screening program aimed at discovering novel anticancer agents based on natural products led to the selection of koningic acid (KA), known as a potent inhibitor of glycolysis. A method was set up to produce this fungal sesquiterpene lactone in large quantities by fermentation, thus allowing (i) an extensive analysis of its anticancer potential in vitro and in vivo and (ii) the semi-synthesis of analogues to delineate structure-activity relationships. KA was characterized as a potent, but non-selective cytotoxic agent, active under both normoxic and hypoxic conditions and inactive in the A549 lung cancer xenograft model. According to our SAR, the acidic group could be replaced to keep bioactivity but an intact epoxide is essential. |
| Databáze: | OpenAIRE |
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