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Bioorg Med Chem. 2015 Jul 1;23(13):3712-21. doi: 10.1016/j.bmc.2015.04.004. Epub 2015 Apr 9.

Anticancer activity of koningic acid and semisynthetic derivatives.

Author information

1
Institut de Recherche Pierre Fabre, Centre de Recherche et Développement, 3 Avenue Hubert Curien-BP 13562, 31035 Toulouse cedex 1, France. Electronic address: nicolas.rahier@pierre-fabre.com.
2
Institut de Recherche Pierre Fabre, Centre de Recherche et Développement, 3 Avenue Hubert Curien-BP 13562, 31035 Toulouse cedex 1, France.
3
Piramal Enterprises Limited, 1 Nirlon Complex, Off Western Express Highway, Goregaon East, Mumbai, Maharashtra 400 063, India.
4
Antitumoral Pharmacology Unit, Centre Oscar Lambret, Inserm U908, BP 307, 59020 Lille cedex, France.
5
Institut de Recherche Pierre Fabre, Centre de Recherche et Développement, 3 Avenue Hubert Curien-BP 13562, 31035 Toulouse cedex 1, France. Electronic address: christian.bailly@pierre-fabre.com.

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.

KEYWORDS:

Cancer; GAPDH; Glycolysis; Koningic acid; Natural products; Semisynthesis

PMID:
25937235
DOI:
10.1016/j.bmc.2015.04.004
[Indexed for MEDLINE]

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