Isolation, Structure Determination of Sesquiterpenes from <i>Neurolaena lobata</i> and Their Antiproliferative, Cell Cycle Arrest-Inducing and Anti-Invasive Properties against Human Cervical Tumor Cells
Andrea Vasas,
Ildikó Lajter,
Norbert Kúsz,
Sándor Balázs Király,
Tibor Kovács,
Tibor Kurtán,
Noémi Bózsity,
Nikolett Nagy,
Zsuzsanna Schelz,
István Zupkó,
Georg Krupitza,
Richard Frisch,
Attila Mándi,
Judit Hohmann
Affiliations
Andrea Vasas
Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary
Ildikó Lajter
Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary
Norbert Kúsz
Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary
Sándor Balázs Király
Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary
Tibor Kovács
Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary
Tibor Kurtán
Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary
Noémi Bózsity
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
Nikolett Nagy
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
Zsuzsanna Schelz
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
István Zupkó
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
Georg Krupitza
Clinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Richard Frisch
Institute for Ethnobiology, Playa Diana, San José GT-170, Petén, Guatemala
Attila Mándi
Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary
Judit Hohmann
Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary
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, 13C and 1H 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.
