Leishmanicidal Effects of Piperlongumine (Piplartine) and Its Putative Metabolites

Author(s)

Moreira, Fernanda de Lima ^[1] ; Moreira, Marcela de Lima ^[3] ; Pilon, Alan Cesar ^[3] ; Lopes, Norberto Peporine ^[3]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[2] Fundacao Oswaldo Cruz FIOCRUZ MG, Inst Rene Rachou, Belo Horizonte, MG - Brazil

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, NPPNS, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Planta Medica; v. 84, n. 15, p. 1141-1148, OCT 2018.
• Web of Science Citations: 2

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 IC (50) values of piperlongumine in promastigote forms of Leishmania infantum and Leishmania amazonensis were 7.9 and 3.3 mu M, respectively. The IC (50) value of piperlongumine in the intracellular amastigote form of L.amazonensis was 0.4 mu M, 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. (AU)

• FAPESP's process: 14/50265-3 - Distribution and metabolism of natural and synthetic xenobiotics: from the comprehension of reactional process to tissue imaging generation
• Grantee: Norberto Peporine Lopes
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 13/04188-4 - In vitro metabolism study and enzymatic inhibition of natural product piplartine employing human liver microsomes and supersomes.
• Grantee: Fernanda de Lima Moreira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/17658-9 - Development and validation of chromatographic and electrophoretic methods for subsequent application in studies of in vitro metabolism and biotransformation - phase 2
• Grantee: Anderson Rodrigo Moraes de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/13292-8 - Analysis of nitrogen content in antropic influenced areas in Amazon and Atlantic Forest using a metabolomic tools
• Grantee: Alan Cesar Pilon
• Support Opportunities: Scholarships in Brazil - Post-Doctoral