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Chamazulene Carboxylic Acid and Matricin: A Natural Profen and Its Natural Prodrug, Identified through Similarity to Synthetic Drug Substances

2006; American Chemical Society; Volume: 69; Issue: 7 Linguagem: Inglês

10.1021/np0601556

1520-6025

Mai Ramadan, Susanne Goeters, Bernhard Watzer, Eva Krause, Klaus Lohmann, Rudolf Bauer, Bernd Hempel, Peter Imming,

Plant Toxicity and Pharmacological Properties

Chamazulene carboxylic acid (1) is a natural profen with anti-inflammatory activity and a degradation product of proazulenic sesquiterpene lactones, e.g., matricin. Both 1 and proazulenes occur in chamomile (Matricaria recutita), yarrow (Achillea millefolium), and a few other Asteraceae species. It was isolated in improved yields, characterized physicochemically, and found to be an inhibitor of cyclooxygenase-2, but not of cyclooxygenase-1. It had anti-inflammatory activity in several animal models with local and systemic application. When human volunteers were given matricin orally, plasma levels of 1 were found to be in the micromolar range. Matricin was converted to 1 in artificial gastric fluid, but not in artificial intestinal fluid. Matricin and the yarrow proazulenes are proposed to be anti-inflammatory through conversion to 1. Intriguingly, the biological activity of the natural compound 1 was found because of its similarity to fully synthetic drug substances. This is the reverse process of the common lead function of natural compounds in drug discovery.