Anticancer activity of koningic acid and semisynthetic derivatives. Issue 13 (1st July 2015)

• Record Type: Journal Article
• Authors: Rahier, Nicolas J.; Molinier, Nicolas; Long, Christophe; Deshmukh, Sunil Kumar; Kate, Abhijeet S.; Ranadive, Prafull; Verekar, Shilpa Amit; Jiotode, Mangesh; Lavhale, Rahul R.; Tokdar, Pradipta; Balakrishnan, Arun; Meignan, Samuel; Robichon, Céline; Gomes, Bruno; Aussagues, Yannick; Samson, Arnaud; Sautel, François; Bailly, Christian
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 13(2015)
• Page Start: 3712
• Page End: 3721
• Publication Date: 2015-07-01
• Subjects: Koningic acid -- Natural products -- Semisynthesis -- Cancer -- GAPDH -- Glycolysis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.04.004
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.