| Literature DB >> 25937235 |
Nicolas J Rahier1, Nicolas Molinier2, Christophe Long2, Sunil Kumar Deshmukh3, Abhijeet S Kate3, Prafull Ranadive3, Shilpa Amit Verekar3, Mangesh Jiotode3, Rahul R Lavhale3, Pradipta Tokdar3, Arun Balakrishnan3, Samuel Meignan4, Céline Robichon2, Bruno Gomes2, Yannick Aussagues2, Arnaud Samson2, François Sautel2, Christian Bailly5.
Abstract
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.Entities:
Keywords: Cancer; GAPDH; Glycolysis; Koningic acid; Natural products; Semisynthesis
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Year: 2015 PMID： 25937235 DOI： 10.1016/j.bmc.2015.04.004
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641