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

Andrea Vasas,Tibor Kovács,Norbert Kúsz,Richard Frisch,Ildikó Lajter,Attila Mándi,Zsuzsanna Schelz,Sándor Balázs Király,István Zupkó,Noémi Bózsity,Georg Krupitza,Judit Hohmann,Nikolett Nagy,Tibor Kurtán

doi:10.3390/pharmaceutics13122088

Andrea Vasas, Tibor Kovács + Show 12 more

Open Access

https://doi.org/10.3390/pharmaceutics13122088

Copy DOI

Abstract

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.

Highlights

This paper reports the isolation and structure elucidation of seven new
The high-resolution MS spectra were acquired on a Thermo Scientific Q-Exactive Plus orbitrap mass spectrometer equipped with ESI ion source in positive ionization mode
Data acquisition and analysis were accomplished with Xcalibur software version 2.0 (Thermo Fisher Scientific, Waltham, MA, USA)

Summary

Introduction

Sesquiterpene lactones (SLs) are one of the most prevalent and biologically significant classes of secondary metabolites of plants, comprising over 5000 known compounds. They are common in several families (e.g., Apiaceae, Solanaceae, Cactaceae and Euphorbiaceae), but the majority of them have been obtained from Asteraceae [1,2]. These lactones are classified biogenetically, according to the carbocyclic skeleton into four main groups: germacranolides, eudesmanolides, guaianolides and pseudoguaianolides.

Objectives

Results

Conclusion