Anthecotulide:  Purification, Analytical Data, Absence from Chamomile Preparations, Stability and Reactivity, and Anti-infective Testing

Abstract

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.

Natural sesquiterpenoids

“…18 The structure of anthecotulide has been confirmed, its NMR data assigned and its stability, reactivity and antibacterial activity evaluated. 19 This major constituent of Anthemis cotula is one of the most potent contact allergens. Recently its biosynthesis has been studied showing that farnesyl diphosphate is not one of its precursors.…”

Anthecotulide Sesquiterpene Lactone Exhibits Selective Anticancer Effects in Human Malignant Melanoma Cells by Activating Apoptotic and Autophagic Pathways, S-Phase Cell Cycle Arrest, Caspase Activation, and Inhibition of NF-κB Signalling Pathway

“…A number of SLs have been reported to exhibit significant anticancer activity and many SQLs are currently undergoing clinical trials [4]. Anthecotulide is an important SQL, but there have been few studies of the anticancer activity of anthecotulide [5]. The present study was designed to examine the anticancer effects of anthecotulide on human malignant melanoma cells.…”

Catalytic Asymmetric Synthesis of (+)-Anthecotulide Using Enyne and Meyer–Schuster Rearrangements

“…At the time, the structure was assigned from analysis of spectroscopic data. In 2005, a more detailed analysis, which included a NOESY experiment to determine the configuration of the stereogenic double bond, corroborated the original structural assignment . Anthecotulide has attracted interest due to its contact allergen properties (contamination of chamomile preparations by A. cotula is to be avoided) and its unusual biosynthesis for a sesquiterpene, involving head-to-middle coupling of geranyl diphosphate and dimethylallyl diphosphate .…”

“…In 2005, a more detailed analysis, which included a NOESY experiment to determine the configuration of the stereogenic double bond, corroborated the original structural assignment . Anthecotulide has attracted interest due to its contact allergen properties (contamination of chamomile preparations by A. cotula is to be avoided) and its unusual biosynthesis for a sesquiterpene, involving head-to-middle coupling of geranyl diphosphate and dimethylallyl diphosphate . More recently, anthecotulide demonstrated antibacterial, antimalarial, trypanocidal, and leishmanicidal activity and has been shown to inhibit the activation pathway of the transcription factor NF- k B which regulates pro-inflammatory mediators (cytokines, nitric oxide, prostaglandins)…”