Isolation, Structure Determination of Sesquiterpenes from Neurolaena lobata and Their Antiproliferative, Cell Cycle Arrest-Inducing and Anti-Invasive Properties against Human Cervical Tumor Cells.

Seven new germacranolides ( 1 - 3 , 5 - 8 ), among them a heterodimer ( 7 ), and known germacranolide ( 4 ), eudesmane ( 9 ) and isodaucane ( 10 ) sesquiterpenes were isolated from the aerial parts of Neurolaena lobata . Their structures were determined by using a combination of different spectroscopic methods, including HR-ESIMS and 1D and 2D NMR techniques supported by DFT-NMR calculations. The enantiomeric purity of the new compounds was investigated by chiral HPLC analysis, while their absolute configurations were determined by TDDFT-ECD and OR calculations. Due to the conformationally flexible macrocycles and difficulties in assigning the relative configuration, 13 C and 1 H NMR chemical shift and ECD and OR calculations were performed on several stereoisomers of two derivatives. The isolated compounds ( 1 - 10 ) were shown to have noteworthy antiproliferative activities against three human cervical tumor cell line with different HPV status (HeLa, SiHa and C33A). Additionally, lobatolide C ( 6 ) exhibited substantial antiproliferative properties, antimigratory effect, and it induced cell cycle disturbance in SiHa cells.