Sesquiterpene Lactones from Calea pinnatifida: Absolute Configuration and Structural Requirements for Antitumor Activity.

Lhaís Araújo Caldas,João H G Lago,Andrea N L Batista,Mariana T Rodrigues,Marcelo J P Ferreira,Patricia Sartorelli,João M Batista,Ileana G S Rubio

doi:10.3390/molecules25133005

Abstract

This work describes the chromatographic fractionation of the aerial parts of Calea pinnatifida and the structural characterization and determination of the absolute configuration of the isolated compounds as well as their antitumor potential. The HPLC fractionation of the CH2Cl2 phase of the MeOH extract from the leaves of C. pinnatifida led to the isolation of two related sesquiterpene lactones (STLs): calein C (1) and calealactone B (2). Additionally, during the purification process, a derivative of calein C (3) was formed as a product of the Michael addition of MeOH. The structures of Compounds 1–3 were established based on spectroscopic and spectrometric data, while the absolute stereochemistry was established by vibrational circular dichroism. In order to evaluate the effect of the conjugated double bonds on the cytotoxic activity of STLs, Compounds 1–3 were tested against anaplastic (KTC-2) and papillary (TPC-1) thyroid carcinoma cells. Calein C was the most active of the STLs, and displayed activity against both KTC-2 and TPC-1. On the other hand, the calein C derivative (3) was the least cytotoxic of all the compounds tested. These results are promising and suggest the importance of studying sesquiterpene lactones isolated from C. pinnatifida in terms of antitumor activity, especially considering the effects of α,β-unsaturated carbonyl systems.

Highlights

Introduction(Asteraceae), popularly known as aruca, cipó cruz or quebra-tudo, occurs in Brazil, mainly in the “cerrado” biome [1]
The presence of α,β-unsaturated carbonyl systems in sesquiterpene lactones (STLs) has been described as an important structural feature responsible for bioactivity, since they are capable of acting as Michael acceptors when in contact with biological nucleophiles [5,6]
On the expressive bioactivity of related sesquiterpene lactones, this work aims to evaluate the cytotoxic potential of STLs isolated from C. pinnatifida against thyroid tumor cell lines, exploring the differences observed between structures in terms of the presence of α,β-unsaturated carbonyl systems

Summary

Introduction

(Asteraceae), popularly known as aruca, cipó cruz or quebra-tudo, occurs in Brazil, mainly in the “cerrado” biome [1]. This species is used in folk medicine as infusions to treat stomachaches, giardiasis, amoebiasis and gastric disorders in general [2]. The presence of α,β-unsaturated carbonyl systems in STLs has been described as an important structural feature responsible for bioactivity, since they are capable of acting as Michael acceptors when in contact with biological nucleophiles [5,6]. Michael acceptor compounds are considered important alkylating agents, capable of supporting alkylation reactions through adequate nucleophiles [7]

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