Sesquiterpene lactones from Gynoxys verrucosa and their anti-MRSA activity

Abstract

Ethnopharmacological relevance 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 (Asteraceae), an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds. Materials and Methods The sesquiterpene lactones leucodine (1) and dehydroleucodine (2) were extracted and purified from the aerial parts of G. verrucosa, and their structure was elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of G. verrucosa extracts and its purified constituents was determined against six clinical isolates including S. aureus and Staphylococcus epidermidis strains with different drug-resistance profiles, using the microtiter broth method. Results Compound 1 has very low activity, while compound 2 has moderate activity with MIC50s between 49 and195 μg/mL. The extract of G. verrucosa has weak activity with MIC50s between 908 and 3290 μg/mL. Conclusions We are reporting the full assignment of the 1H-NMR and 13C-NMR of both compounds, and the crystal structure of compound 2, for the first time. Moreover, the fact that compound 2 has antimicrobial activity and compound 1 does not, demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones. However, the weak activity observed for the plants extracts, does not explain the use of G. verrucosa in traditional medicine for the treatment of wounds and skin infections.

Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation

“…verrucosa was extracted with methanol at room temperature, which was followed by evaporation of the solvent in a vacuum. Dehydroleucodine was isolated and characterized ( S1 Fig ), as previously described [ 6 ]. Dehydroleucodine stock solutions (1000 μM) were prepared with dimethylsulfoxide (DMSO) 100% and stored at -20°C.…”

“…One member of the Asteraceae family, the plant Gynoxys verrucosa Wedd, which is known as “guángalo” or “congona”, is a shrub grown in the provinces of Loja and Zamora-Chinchipe and has been used by the indigenous population of South America (e.g., Ecuador, Columbia, Peru) for medicinal purposes for ages [ 5 ]. Among the secondary metabolites isolated from this species is the sesquiterpene lactone Dehydroleucodine (DhL), which possesses anti-inflammatory, anti-parasitic and anti-microbial activities [ 6 – 9 ]. The main goal of this work was to determine whether DhL may display cytostatic, cytotoxic and genotoxic activities on human cancer cells.…”

A review on medicinal plant extracts and their active ingredients against methicillin-resistant and methicillin-sensitive Staphylococcus aureus

“…Purification of this fraction gave four compounds; the compound 4 (6E, 12E)-tetradecadiene-8, 10-diyne-1, 3-diol) possessed anti-MRSA activity at a MIC value of 4-32 μg/mL. These results provide a promising basis for the potential use of this extract as well as the separation of its compounds for the treatment of bacterial infections (58).…”

Biomedical Properties and Origins of Sesquiterpene Lactones, with a Focus on Dehydroleucodine

“…In addition, it has also been shown to be active against H. pylori strains [118]. Recent work has also shown 3 to be active against methicillin resistant S. aureus (MRSA) and S. epidermis (MRSE), respectively [119]. These observations show that both 1 and α-βunsaturated moieties are structurally necessary for the observed therapeutic effects although other structural moieties may also be required.…”

“…Additional anti-microbial activity was found with in vitro treatment with dehydroleucodine of Staphylococcus aureus and S. epidermidis [130]. The lactone ring of 3 was found to be essential for this antimicrobial activity [130].…”