Antileishmanial activity of diterpene acids in copaiba oil

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 (IC 50 ) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC 50 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.

Production of Phytotherapeutics in Brazil: History, Problems and Perspectives

“…O seuà leoà e aà e ele teà pa aà aà u aà deà feridas, porque nem mesmo restam vestígios deà i at izes ,à dizà eleà p gi aà .à Ga ielà Soares de Sousa 60 oà o side avaà u à leoà sa tíssi o à ta à usadoà pa aà f ialdades,à dores de barriga e po tadasà deà f io à p gi aà 164). Para Gândavo 49 ,antiinflamatória [261][262][263][264][265][266][267] , antileishmania [268][269][270][271] , na endometriose 272 , na urolitíase 273 , na acne 274 , na psoríase 275 , no controle do mosquito Aedes aegypti [276][277][278] , no controle de ácaros 279 e em infecções ginecológicas. 280 O óleo da copaíba também reduz os níveis séricos de ureia e creatinina em ratos submetidos à síndrome de isquemia e reperfusão.…”

Anti-Trypanosoma Activity and Synergistic Effects of Natural and Semi-Synthetic Triterpenes and Predominant Cell Death through Autophagy in Amastigote Forms

“…Furthermore, different classes of terpenes have been demonstrated desirable synergistic effects when combined, since drug combination may improve the parasitic activity with lower dosage of these substances, in addition to reducing their undesirable toxic effects. [11][12][13][14][15][16][17] The search for synergic compounds can improve the efficiency of the treatment, reduce their toxicities on mammalian cells and diminish the selection of resistant mutations. 12,[18][19][20] Alternative strategies have been designed to identify candidates among the already available drugs in the market that could be used in combination to provide synergic effects and improve the chemotherapy efficacy.…”

Antitubercular Activity Increase in Labdane Diterpenes from Copaifera Oleoresin through Structural Modification

“…This turns them an interesting source of natural products to be isolated and assayed against different pathological agents. [16][17][18] Terpenoids are one of the largest classes of natural products, 12 and some of them are widely used as starting materials in natural products synthesis. 16 Some diterpenes displayed a remarkable antitubercular activity against M. tuberculosis, despite the fact that only a limited number of them were assayed against this pathogenic agent.…”