Antileishmanial activity of crude extract and coumarin from Calophyllum brasiliense leaves against Leishmania amazonensis

Abstract

Infections by protozoans of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which show renal and cardiac toxicity. As part of a search for new drugs against leishmaniasis, we evaluated the in vitro leishmanicidal activity of the (-) mammea A/BB. The compound (-) mammea A/BB is a coumarin-type mammea purified from a dichloromethane crude extract of leaves of Calophyllum brasiliense Cambess (Clusiaceae). The isolated compound was characterized using spectral analyses by UV, infrared, nuclear magnetic resonance of (1)H, (13)C, distortionless enhancement by polarization transfer, correlation spectroscopy, heteronuclear multiple bond correlation, and heteronuclear multiple quantum coherence. The compound (-) mammea A/BB showed significant activity against promastigote and amastigote forms of L. amazonensis, with IC(50) (50% inhibition concentration of cell growth) at a concentration of 3.0 and 0.88 mug/ml and IC(90) (90% inhibition concentration of cell growth) of 5.0 and 2.3 microg/ml, respectively. The coumarin (-) mammea A/BB showed no cytotoxicity against J774G8 macrophages in culture, when it was tested at high concentrations that inhibited promastigote forms. Electron microscopy studies revealed considerable ultrastructural changes when promastigote forms of L. amazonensis were treated with 3.0 microg/ml of the coumarin (-) mammea A/BB for 72 h. We observed significant changes such as mitochondrial swelling with concentric membranes in the mitochondrial matrix and intense exocytic activity in the region of the flagellar pocket. Other alterations included the appearance of binucleate cells and multiple cytoplasmic vacuolization. These results showed that (-) mammea A/BB is a potent growth inhibitor of L. amazonensis and caused important changes in the parasite's ultrastructure. This study provided new perspectives on the development of novel drugs with leishmanicidal activity obtained from natural products.

Antileishmanial activity of leaf extract from Calophyllum rivulare against Leishmania amazonensis

“…However, some extracts from other species of the genus Calophyllun have been evaluated against Leishmania and other microorganisms. The dichloromethane crude extract from leaves of C. brasiliense showed a significant in vitro (Honda et al, 2010;Brenzan et al, 2007) and in vivo activity against L. amazonensis (Honda et al, 2010). A coumarin was isolated from this extract and its derivatives showed significant activity against L. amazonensis, with IC 50 between 0.6 and 34.0 µg/mL (Brenzan et al, 2007;Brenzan et al, 2008).…”

“…The dichloromethane crude extract from leaves of C. brasiliense showed a significant in vitro (Honda et al, 2010;Brenzan et al, 2007) and in vivo activity against L. amazonensis (Honda et al, 2010). A coumarin was isolated from this extract and its derivatives showed significant activity against L. amazonensis, with IC 50 between 0.6 and 34.0 µg/mL (Brenzan et al, 2007;Brenzan et al, 2008). On other hand, the extract from roots of C. brasiliense was active against L. chagasi and Plasmodium falciparum, with an IC 50 of 6.7 and 27.6 g/mL, respectively (Albernaz et al, 2010).…”

Antileishmanial Activity of Coumarin from Amburana cearensis Seeds

“…To evaluate the antileishmanial activity of coumarin (-) mammea A/BB isolated from extracts of the leaves of Calophyllum brasiliensis, L. amazonensis promastigotes were challenged with 3.0 mg/mL (-) mammea A/BB for 72 hours. On electron microscopy, ultrastructural changes were observed, including binucleated cells, multiple vacuolation, intense exocytic activity in the flagellar pocket region and swollen mitochondria with concentric membranes in the mitochondrial matrix [20].…”

Leishmanicidal activities of the extract from Blepharocalyx salicifolius (Kunth) O. Berg, Myrtaceae

“…Several studies has been carried out using natural products as a source to obtain species that can be used as a target in treatment of leishmaniasis (Rao et al, 2004;Ayres et al, 2007;Dube et al, 2007), mainly from vegetal source (Rocha et al, 2005;Muzitano et al, 2006;Braga et al, 2007;Brenzan et al, 2007;Soares et al, 2007). These studies look at to increase the therapeutic arsenal, because there is a lack of effective and safety medicines.…”