A simulation study of the interaction of sulfhydryl nucleophiles with several antifungal sesquiterpene lactones isolated from Greek Centaurea sp.

Sesquiterpene lactones are terpenoid compounds characteristic of the Asteraceae (Compositae) possessing a variety of biological activities, such as cytotoxic, antitumor, antibacterial and antifungal. It is well known that the activity of a given sesquiterpene lactone may be determined by the availability and accessibility of vitally important thiol compounds present in specific fungi, such as cysteine and glutathione. A simulation study of the interaction of the sulfhydryl nucleophiles with two germacranolides, selected from a series of natural antifungal sesquiterpene lactones and corresponding semi-synthetic derivatives, was performed through molecular modeling techniques. The Hartree-Fock ab initio calculations revealed that structural modification of the examined natural sesquiterpene lactones may increase their biologic activity.