Sesquiterpene lactones sites

Most biological activities of STLs have been related to the presence of electrophilic structure elements, which undergo covalent reaction with functional biological macromolecules resulting in their deactivation [1-3]. In this respect, a,P-unsaturated carbonyl groups as well as epoxide and free aldehyde groups have to be considered reactive partial structures. The alkylation of free cysteine residues in enzymes and other functional proteins by STLs has in many instances been held responsible for STL bioactivity and there is a clear correlation between the presence of such residues in proteins and their susceptibility to inactivation by STLs [1-3], see section Alkylant Sesquiterpene Lactones . It was therefore of interest to investigate the distribution of such potential reactive sites (PRS) in the structures of the 4861 STLs (Table 1). 

Our own work on structure-activity relationships of convulsant sesquiterpene lactones was initiated after isolation of a variety of seco-prczizaanc type compounds from Illicium floridanum and I. parviflorum, both endemic to the southern United States [157, 179-181]. A study on the in-vivo toxicity of several of these compounds [182] showed that anisatin, major constituent in leaves and fruits of I. floridanum (as in those of other previously studied toxic Illicium (=star anise) species, review see [3]), was apparently the only derivative in the tested series which was toxic to mammals, although further compounds, such as pseudoanisatin (PSA, structure 4 in Fig. (27)) were accumulated in the plant in similarly high amounts [179, 180]. In the light of reports that indicated an identical mechanism of action and -possibly- the existence of a common binding site for anisatin and picrotoxinin [156-161] the question arose which structural features in these compounds were similar enough to warrant an identical mode of molecular recognition at the channel protein. 

In this test, a dye of Dansyl chloride [5-(dimethylamino)naphthalene-1-sulphonyl chloride] is apphed to the skin leaving a dye stain which disappears proportionally with the characteristic power of the apphed preparation to induce the formation of new cells which displace the dye colored cells. The preparation (0.2% sesquiterpene lactones) was compared to a standard 2% a-hydroxy-acid lotion (known to be a potent cell renewal agent). The extract gave a 50% reduction in the stain as compared to the untreated site of the skin after 11 days while the standard preparation gave only 38% reduction after the same period of time (Table 2 and Figure 8). This means that the 50% cell... 

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