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Planta Med 2018; 84(15): 1141-1148
DOI: 10.1055/a-0614-2680
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Leishmanicidal Effects of Piperlongumine (Piplartine) and Its Putative Metabolites

Fernanda de Lima Moreira
1   Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto – SP, Brazil
,
Thalita Bachelli Riul
2   Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto – SP, Brazil
,
Marcela de Lima Moreira
3   Instituto René Rachou, Fundação Oswaldo Cruz – FIOCRUZ/MG, Belo Horizonte – MG, Brazil
,
Alan Cesar Pilon
4   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto –SP, Brazil
,
Marcelo Dias-Baruffi
2   Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto – SP, Brazil
,
Márcio S. S. Araújo
3   Instituto René Rachou, Fundação Oswaldo Cruz – FIOCRUZ/MG, Belo Horizonte – MG, Brazil
,
Norberto Peporine Lopes
4   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto –SP, Brazil
,
Anderson R. M. de Oliveira
5   Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto – SP, Brazil
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Weitere Informationen

Publikationsverlauf

received 14. Oktober 2017
revised 05. April 2018

accepted 15. April 2018

Publikationsdatum:
15. Mai 2018 (online)

    Lizenzen und Reprints

Abstract

Piperlongumine is an amide alkaloid found in Piperaceae species that shows a broad spectrum of biological properties, including antitumor and antiparasitic activities. Herein, the leishmanicidal effect of piperlongumine and its derivatives produced by a biomimetic model using metalloporphyrins was investigated. The results showed that IC50 values of piperlongumine in promastigote forms of Leishmania infantum and Leishmania amazonensis were 7.9 and 3.3 µM, respectively. The IC50 value of piperlongumine in the intracellular amastigote form of L. amazonensis was 0.4 µM, with a selectivity index of 25. The piperlongumine biomimetic derivatives, Ma and Mb, also showed leishmanicidal effects. We also carried out an in vitro metabolic degradation study showing that Ma is the most stable piperlongumine derivative in rat liver microsome incubations. The results presented here indicate that piperlongumine is a potential leishmanicidal candidate and support the biomimetic approach for development of new antileishmanial derivatives.

Key words

cyclic amides - piplartine - metalloporphyrin - leishmaniasis - selectivity index - piperlongumine - Piperaceae - analogues

Supporting Information

    Biomimetic reaction conditions tested, HPLC chromatograms in analytical and semipreparative scales for the reaction selected, MS and NMR spectra of Ma and Mb, and IC50s of AMPH in L. amazonensis and L. infantum promastigotes are available as Supporting Information.

  • Supporting Information
 

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