Toxic activities of sesquiterpene lactones: Structural and biochemical aspects

As one of the largest groups of secondary plant metabolites, sesquiterpene lactones (STL) possess a broad variety of conspicuous biological activities directed towards all types of predating organisms. The majority of these c ompounds are believed to exert their activities by a common chemical mechan ism of action, alkylation of biological macromolecules leading to decisive consequences on cellular function. An impressive number of enzymes and othe r essential macromolecules are known to be inhibited by STL, usually at ver y low concentrations. Such alkylant STL, therefore, are generally cytotoxic . Although many of them possess potentially useful activities, e.g, as ther apeutic agents against inflammation and cancer, the low selectivity of thes e effects usually forbids utilization due to high unspecific toxicity. In a ddition to such alkylants which can be considered a non-specific and highly efficient chemical weapon against literally any organism that might be har mful to the plants, some less common representatives which exert toxicity b y very specific molecular mechanisms, such as some strong inhibitors of int racellular calcium signalling and some highly potent GABA-antagonistic neur otoxins, are treated separately. The various aspects of sesquiterpene lactone toxicity from the general chem ical basis via molecular targets and toxic effects at the cellular level to toxicity versus the different mammalian organ systems are outlined. Wherev er possible, special attention is paid to relationships between chemical st ructure and bioactivity.