Evaluation of in vitro activity and ultrastructural changes in Leishmania amazonensis caused by sesquiterpene lactones from Calea pinnatifida (Asteraceae)

Calea genus, belonging to the Asteraceae, is composed by approximately 125 species. Some of these species were chemically investigated and sesquiterpene lactones as well as furan sesquiterpenes have been identified [1]. There are several biological activities related to the compounds present in the genus Calea, such as anti-inflammatory, antiplasmodial, antifungal, antimicrobial and cytotoxic, which are credited to the presence of sesquiterpene lactones, mainly germacranolide derivatives [2]. C. pinnatifida, popularly known as "aruca" and “cipó-cruz”, has been encountered specially in Brazilian Cerrado biome (“savanna like”) and has been used in folk medicine to treat stomachaches, giardiasis and amebiasis. In Brazil this species is commercially available in popular market as an ethanol extract of the leaves to treat amoebic dysentery. Chemically, the aerial parts are composed of fatty esters, glycoside of p-hydroxybenzoic acid, anisic acid, sitosterol, stigmasterol, polyacetylene derivatives and germacranolides [3]. Previous studies revealed germacranolides displayed cytotoxic potential inducing apoptosis in different tumor cells, as well as displayed inhibitory activity of NF-κB factor [4]. In present work, the bioactivity guided fractionation of crude ethanol extract from leaves of C. pinnatifida led to isolation of two sesquiterpene lactones: arucanolide and calealactone C, which structures were established on the basis of spectroscopic analysis. These compounds displayed potent activity against promastigote forms of Leishmania (L.) amazonensis with EC₅₀ of 1.7 and 4.6 µg/mL to arucanolide and calealactone C, respectively. These compounds caused ultrastructural changes in L. amazonensis promastigotes leading to a loss of their classical structural morphology, as evidenced by electron microscopy. Additionally, calealactone C presented low cytotoxicity for J774 macrophages (CC₅₀ 31.73 µg/mL), similar to positive controls and presented antiamastigote activity with EC₅₀ of 4.24 µg/mL.

Acknowledgements: The authors would like to thank FAPESP and CNPq for providing financial support to this study.

Keywords: Calea pinnatifida, sesquiterpene lactones, arucanolide, calealactone C, antileishmanial activity, ultrastructural changes.

References:

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