Sesquiterpene Lactones of Gynoxys verrucosa and their Anti-MRSA Activity

Because of its virulence and antibiotic resistance, Staphylococcus aureus is a more formidable pathogen now than at any time since the pre-antibiotic era. In an effort to identify and develop novel antimicrobial agents with activity against this pathogen, we have examined Gynoxys verrucosa Wedd, an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds. Phytochemical investigation of the ethyl-acetate extract of the aerial parts of G. verrucosa led to the isolation of two known sesquiterpene lactones leucodine (1) and dehydroleucodine (2). We assayed G. verrucosa extracts and their constituents, 1 and 2, against methicillin-resistant S. aureus and other Gram positive bacteria. The structures of compounds 1 and 2 were elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of G. verrucosa extract and its isolates was determined against six clinical isolates including Staphylococcus aureus and S. epidermidis strains with different drug-resistance profiles, using the microtiter broth method. The results show that compound 1 showed very low activity, while compound 2 and the G. verrucosa extract have activity against the microorganism, with MICs between 49–195 and 320–908µg/mL, respectively. These results suggest that the use of G. verrucosa in traditional medicine for the treatment of wounds and skin infections, especially those with a staphylococcal causation, is justified. Moreover, the fact that compound 1 showed very low bioactivity demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones.