Leishmanicidal Effects of Piperlongumine (Piplartine) and Its Putative Metabolites

Fernanda de Lima Moreira; Thalita Bachelli Riul; Marcela de Lima Moreira; Alan Cesar Pilon; Marcelo Dias-Baruffi; Márcio S. S. Araújo; Norberto Peporine Lopes; Anderson R. M. de Oliveira

doi:10.1055/a-0614-2680

Planta Medica, Table of Contents

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

Authors

Fernanda de Lima Moreira

¹Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto – SP, Brazil
Thalita Bachelli Riul

²Departamento 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

³Instituto René Rachou, Fundação Oswaldo Cruz – FIOCRUZ/MG, Belo Horizonte – MG, Brazil
Alan Cesar Pilon

⁴Núcleo 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

²Departamento 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

³Instituto René Rachou, Fundação Oswaldo Cruz – FIOCRUZ/MG, Belo Horizonte – MG, Brazil
Norberto Peporine Lopes

⁴Núcleo 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

⁵Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto – SP, Brazil

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

Full Text

References

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