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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


Publikationsverlauf

Eingereicht: 08. Juli 2020

Angenommen nach Revision: 17. Oktober 2020

Artikel online veröffentlicht:
23. November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Missouri Botanical Garden. Tropicos.org. Perezia multiflora . Accessed August 25, 2020 at: https://www.tropicos.org/name/2701110
    PubMed
  • 2 Mostacero-León J, Castillo-Picón F, Mejía-Coico FR, Gamarra-Torres OA, Charcape-Ravelo JM, Ramirez-Vargas RA. Plantas medicinales del Perú, 1 ed. Trujillo: Asamblea Nacional de Rectores; 2011
    Suche in Google Scholar
  • 3 Bohlmann F, Zdero C. Neue Sesquiterpene mit anomalem Kohlenstoffgerüst aus der Tribus Mutisieae . Chem Ber 1979; 112: 427-434
    CrossrefPubMedSuche in Google Scholar
  • 4 Bohlmann F, Zdero C. Über eine neue Gruppe von Sesquiterpenlactonene aus der Gattung Trixis . Chem Ber 1979; 112: 435-444
    CrossrefPubMedSuche in Google Scholar
  • 5 Bohlmann F, Zdero C, King RM, Robinson H. A tetracyclic sesquiterpene, further isocedrene, and guaiene derivatives from Jungia stuebelii . Phytochemistry 1983; 22: 1201-1206
    CrossrefPubMedSuche in Google Scholar
  • 6 Singh P, Jakupovic J, Bohlmann F. Isocedrene derivatives and other sesquiterpenes from Moscharia pinnatifida . Phytochemistry 1985; 24: 1525-1529
    CrossrefPubMedSuche in Google Scholar
  • 7 Zdero C, Bohlmann F, Niemeyer HM. Isocedrene and guaiane derivatives from Pleocarphus revolutus . J Nat Prod 1988; 51: 509-512
    CrossrefPubMedSuche in Google Scholar
  • 8 Zdero C, Bohlmann F, Sanchez H, Dominguez XA. Isocedrene derivatives and other constituents from Acourtia nana . Phytochemistry 1991; 30: 2695-2697
    CrossrefPubMedSuche in Google Scholar
  • 9 Zdero C, Bohlmann F, King RM, Robinson H. α-Isocedrene derivatives, 5-methyl coumarins and other constituents from the subtribe Nassauviinae of the Compositae. Phytochemistry 1986; 25: 2873-2882
    CrossrefPubMedSuche in Google Scholar
  • 10 De Riscala EC, Catalan CAN, Sosa VE, Gutierrez AB, Herz W. Trixane derivatives from Trixis praestans . Phytochemistry 1988; 27: 2343-2346
    CrossrefPubMedSuche in Google Scholar
  • 11 Ybarra MI, Catalan CAN, Diaz JG, Herz W. A cyperane and trixanes from Jungia polita . Phytochemistry 1992; 31: 3627-3629
    CrossrefPubMedSuche in Google Scholar
  • 12 Azevedo L, Faqueti L, Kritsanida M, Efstathiou A, Smirlis D, Franchi GCJ, Genta-Jouve G, Michel S, Sandjo LP, Grougnet R, Biavatti MW. Three new trixane glycosides obtained from the leaves of Jungia sellowii less. using centrifugal partition chromatography. Beilstein J Org Chem 2016; 12: 674-683
    CrossrefPubMedSuche in Google Scholar
  • 13 Kotowicz C, Hernandez LR, Cerda-Garcia-Rojas CM, Villecco MB, Catalan CAN, Joseph-Nathan P. Absolute configuration of trixanolides from Trixis pallida . J Nat Prod 2001; 64: 1326-1331
    CrossrefPubMedSuche in Google Scholar
  • 14 Maldonadoa EM, Salamanca E, Gimenez A, Saavedra G, Sterner O. Antileishmanial metabolites from Trixis antimenorrhoea . Phytochem Lett 2014; 10: 281-286
    CrossrefPubMedSuche in Google Scholar
  • 15 Zdero C, Bohlmann F, Solomon J, Dominguez XA. Further isocedrene derivatives and other constituents from Perezia species. Phytochemistry 1988; 27: 849-853
    CrossrefPubMedSuche in Google Scholar
  • 16 Kirby AJ. Stereoelectronic Effects. Oxford: Oxford University Press; 1996
    CrossrefSuche in Google Scholar
  • 17 Lodewyk MW, Siebert MR, Tantillo DJ. Computational prediction of 1H and 13C chemical shifts: a useful tool for natural product, mechanistic, and synthetic organic chemistry. Chem Rev 2012; 112: 1839-1862
    CrossrefPubMedSuche in Google Scholar
  • 18 Castro I, Fabre N, Bourgeade-Delmas S, Saffon N, Gandini C, Sauvain M, Castillo D, Bourdy G, Jullian V. Structural characterization and anti-infective activity of 9, 10-seco-29-norcycloartane glycosides isolated from the flowers of the peruvian medicinal plant Cordia lutea . J Nat Prod 2019; 82: 3233-3241
    CrossrefPubMedSuche in Google Scholar