Sesquiterpenes from Neurolaena lobata with antiproliferative activity

Neurolaena lobata L. (Asteraceae) is a perennial herb native to tropical part of America. It has been used in traditional medicine for the treatment of different types of cancer, ulcers, inflammatory skin disorders and diabetes. The main constituents of the plant are sesquiterpene lactones, which can be responsible for its different pharmacological effects. Our previous studies revealed the presence of sesquiterpenes of the germacranolide, eudesmanolide and furanoheliangolide types, and some of them proved to be active against cancer and inflammation in vitro and in vivo. In continuation of our work, further sesquiterpenes were isolated from N. lobata and their antiproliferative activity was investigated on human cancer cell lines (SiHa, HeLa and C33A, at 10 and 30µM concentrations) using the MTT assay. The aerial parts of the plant were extracted with methanol. After evaporation, the extract 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 PLC. The structure elucidation of the compounds was carried out by means of MS, 1D and 2D NMR spectroscopy. The results allowed the identification of five sesquiterpenes, four of them esterified with isovaleric acid at C-8 or C-9. The new compounds are sesquiterpene lactones, the dimer lobatolide A, the calyculatolide derivative lobatolide B, and the germacranolide-type lobatolides C and D. Furthermore, one known guaiane-type sesquiterpene [(+)-aphanamol I] were also isolated from the plant. With the exception of the known compound, all component possessed remarkable antiproliferative activities (inhibition %± SEM between 60.92 ± 1.73 and 96.45 ± 0.27) on at least two cell lines, at 30µM concentration. Lobatolide A proved to be the most active.

This work was supported by GINOP-2.3.2 – 15 – 2016 – 00012, ÚNKP-16 – 3 and a János Bolyai Research Scholarship of the Hungarian Academy of Sciences.