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Planta Med 2021; 87(03): 201-208
DOI: 10.1055/a-1298-4706
Biological and Pharmacological Activity
Original Papers

Bioactive Isocedrenes from Perezia multiflora

Sandra Bourgeade-Delmas
1   UMR 152 Pharmadev, Université de Toulouse, IRD, UPS, Toulouse, France
,
Christiane André-Barrès
2   UMR 5068 LSPCMIB, Université de Toulouse, CNRS, UPS, Toulouse, France
,
Jeanne Lucas
1   UMR 152 Pharmadev, Université de Toulouse, IRD, UPS, Toulouse, France
,
Manon Trinel
1   UMR 152 Pharmadev, Université de Toulouse, IRD, UPS, Toulouse, France
,
Denis Castillo Pareja
3   Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
,
Valérie Jullian 
1   UMR 152 Pharmadev, Université de Toulouse, IRD, UPS, Toulouse, France
3   Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
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Abstract

Four isocedrenes (1 – 4), including one new compound (2), were isolated from an ethanolic extract of the aerial parts of Perezia multiflora by bioactivity-guided fractionation. For compounds 1 and 3, a revised stereochemical assignment is proposed based on molecular modeling studies using DFT-NMR calculations. Antiparasitic activity of the four compounds was evaluated using an in vitro culture of Plasmodium falciparum and axenic amastigotes of Leishmania infantum. IC50 values ranged from 0.81 to 16.1 µM (P. falciparum) and 0.16 to 2.03 µM (L. infantum). Toxicity was evaluated against J774A.1 mouse macrophages or human macrophages generated from THP-1 monocytic cells (IC50 values ranging from 0.16 to 2.64 µM). Compound 4 exhibited weak selectivity against P. falciparum with a selectivity index (SI = CC50/IC50) of 3. No selectivity was observed for compounds 1 – 3 against both parasites.

Key words

Perezia multiflora - Asteraceae - isocedrenes - sesquiterpenes - Plasmodium - Leishmania

Supporting Information

    Detailed results of DFT calculations and NMR modulizations for compounds 1 – 3, including geometries, total energies, enthalpies, and Boltzmann distribution; experimental (CDCl3) and calculated 13C chemical shifts in the chloroform PCM continuum model (SMD) plus RMSD values; calculated 1H chemical shifts and coupling constants for the major conformers; experimental NOE effects and distances observed on the major conformers; 1H NMR spectrum simulated at 300 MHz using MestReNova software compared to an experimental one in CDCl3; 1H and 13C NMR data in CDCl3 for compounds 1 – 3; 1D and 2D NMR spectra of compounds 1, 2, and 3 in C6D6; ECD spectra of compounds 1 – 3; and dose-response curves used for determination of IC50 values for compounds 1 – 4 and reference compounds are provided as Supporting Information.

  • Supporting Information


Publication History

Received: 08 July 2020

Accepted after revision: 17 October 2020

Article published online:
23 November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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