New sesquiterpenes from Neurolaena lobata

The Maya ethnopharmacological plant Neurolaena lobata (L.) R.Br. ex Cass (Asteraceae) has been widely applied in traditional medicine in Central and South America for the treatment of different types of cancer, ulcers, inflammatory skin disorders and diabetes. The main constituents of the plant were identified as sesquiterpene lactones, which are responsible for its different pharmacological effects. Our previous studies revealed the presence of 13 sesquiterpenes of the germacranolide, eudesmanolide, eudesmane and furanoheliangolide types and some of them were reported as active compounds against cancer and inflammation in vitro and in vivo. In continuation of our studies on this field, the aim of the present work was the isolation and identification of new bioactive sesquiterpenes from N. lobata.

The aerial parts of the plant were extracted with methanol. After evaporation it was subjected to solvent-solvent partition with n-hexane and CH₂Cl₂. The CH₂Cl₂ fraction was chromatographed by a combination of different methods, including CC, VLC and preparative TLC. The structure determinations of the isolated compounds were carried out by means of MS and NMR (1D- and 2D-NMR) spectroscopy.

The results allowed the identification of four new sesquiterpenes, all esterified with isovaleric acid at C-8 or C-9. The new compounds are lobatin E, 8β-hydroxy-9α-isovaleroyloxy-calyculatolide, an unsaturated 1,10-epoxy-germacranolide ester, and an unprecedented non-lactone type 6,10-epoxy-germacranolide ester. Furthermore, one known furanoheliangolide lobatin C, and one known eudesmane type sesquiterpene volenol were also isolated from the plant. In the case of lobatin C, the previously published spectral data were supplemented with complete ¹H- and ¹³C-NMR shift assignments.

Acknowledgement: This work was supported by the Hungarian Scientific Research Fund (OTKA K109846) and a János Bolyai Research Scholarship of the Hungarian Academy of Sciences.