Sesquiterpene lactones (SL) part XXIV. Further studies on cytotoxic activities of SL in tissue culture of human cancer cells

Abstract

Cytotoxicity of most of the 18 new sesquiterpene lactones (SL), derivatives of germacran, guaian, pseudoguaian, and selinan, and related glycosides was studied by tissue culture method on human KB and HeLa cell lines. Eleven compounds with ED50, activity values between 0.24 and 2.40 microgram/ml (9,2.10(-7)--9.1.10(-6) M) were qualified for further in vivo investigation. It seems that: a) unsaturated alpha-exo-methylene-gamma-lactone ring:-O-CO-C=CH2 conjugated with basic terpene carbocyclic skeleton plays the main role for cytotoxicity of SL. The next determinants of the activity are apparently: b) sesquiterpenoid carbocyclic grouping (germacranolides (GE), pseudoguaianolides (PGU), guaianolides (GU), c) the position of cyclization of gamma-lactone ring (C6--C12) or C8--C12), d) some substituents with an epoxide and/or keto-function in different positions of sesquiterpenoids. The natural and modified alpha-exo-methylene-guaianolide-C3-glycosides (GUG) are not significantly more potent than the remaining alpha-exo-methylene-gamma-lactones.