Immunobiological properties of sesquiterpene lactones with specific active diol moiety

Sesquiterpene lactones constitute a large group of plant secondary metabolites, biogenetically belonging to isoprenoids. They possess extensive range of biological activities and are widely abundant in various natural sources.

Effects of sesquiterpene lactones on immunobiological responses triggered by lipopolysaccharide were tested under in vitro conditions using rat and mouse resident peritoneal macrophages. Namely, production of nitric oxide (NO) and secretion of cytokines were investigated. The sesquiterpene lactone thapsigargin, containing specific diol system at their lactone moiety, significantly enhanced not only NO production, but also various other immune functions including in vitro production of interferon-γ on its own [1].

In this work, special consideration was paid to plant sesquiterpene lactones possessing α-exomethylene-γ-lactone moiety, to structurally related natural hydroxyl containing analogues, and to synthetic hydroxy or amino adducts. Relation between the molecular structure and immunobiological activity was investigated. In addition the implication of the diol moiety combined with other structure functionality was assessed. New natural and chemically transformed sesquiterpene lactones, structurally related to thapsigargin, were identified, possessing the same kind of immuno-biological properties.

Acknowledgement: Supported by GACR, grant No. 203/07/1227

Reference: 1. Kmoníčková, E. et al. (2008) Eur. J. Pharmacol., DOI: 10.1016/j.ejphar.2008.03.037