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.
The sesquiterpene lactone anthecotulide (1) was extracted from Anthemis cotula in 0.7% w/w yield. A pure standard was prepared by preparative TLC and used for quantitative determination of 1 with a TLC scanner. The constitution of 1 was corroborated and the double-bond configuration determined. It was stable at room temparature in air and reacted very slowly with glutathione. It was not detectable in 34 chamomile (Matricaria recutita) preparations and did not show antibacterial activity against a range of clinically important strains at a concentration of <10 microg/mL.
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