Antileishmanial activity of diterpene acids in copaiba oil

Adriana Oliveira Dos Santos,Benedito Prado Dias-Filho,Celso Vataru Nakamura,Valdir Florêncio Da Veiga-Júnior,Erika Izumi,Tânia Ueda-Nakamura

doi:10.1590/s0074-02762013000100010

Adriana Oliveira Dos Santos, Benedito Prado Dias-Filho + Show 4 more

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https://doi.org/10.1590/s0074-02762013000100010

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Abstract

Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs.

Highlights

Leishmania is a genus of protozoan parasites that are transmitted by the bite of the sandfly and cause diseases collectively known as leishmaniasis (Kaye & Scott 2011)
Parasites - Promastigote forms of L. amazonensis (WHOM/BR/75/Josefa), which were originally isolated by Cesar Augusto Cuba-Cuba (Universidade de Brasília, Brazil) from a human case of diffuse cutaneous leishmaniasis, were cultured at 25oC in Warren’s medium supplemented with 10% heat-inactivated foetal bovine serum (FBS) (Gibco Invitrogen Corporation, New York, USA) in a tissue flask
The compounds tested were agathic acid, hydroxycopalic acid, kaurenoic acid, methyl copalate, pinifolic acid and polyaltic acid, which were isolated from Copaifera

Summary

Introduction

Leishmania is a genus of protozoan parasites that are transmitted by the bite of the sandfly and cause diseases collectively known as leishmaniasis (Kaye & Scott 2011). According to the World Health Organization (WHO), there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. This disease is endemic in 88 countries, with a total of 350 million people at risk. Parasites - Promastigote forms of L. amazonensis (WHOM/BR/75/Josefa), which were originally isolated by Cesar Augusto Cuba-Cuba (Universidade de Brasília, Brazil) from a human case of diffuse cutaneous leishmaniasis, were cultured at 25oC in Warren’s medium (brain-heart infusion plus haemin and folic acid) supplemented with 10% heat-inactivated foetal bovine serum (FBS) (Gibco Invitrogen Corporation, New York, USA) in a tissue flask. The 50% inhibitory concentration (IC50) was determined by logarithm regression analysis of the data obtained (Santos et al 2012)

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