Effect of the marine brown alga Canistrocarpus cervicornis on promastigote forms of Leishmania (L.) amazonensis

Leishmaniasis is a disease resulting from infection by protozoan parasites of the genus Leishmania. Pentavalent antimonials, used clinically for more than 50 years, are still the first-choice drugs for the treatment of leishmaniasis, but they are toxic, require long-term treatment, and are prone to stimulate drug resistance [1]. Marine brown algae (Phaeophyceae) belonging to the order Dictyotales have emerged as an exceptionally rich source of diterpenoids, which form part of a defensive strategy against herbivores in the marine environment [2]. We have investigated the activity of crude extracts, a fraction, and an isolated compound (4R, 9S, 14S)-4α-Acetoxy-9β,14α-dihydroxydolast-1(15),7-diene of the brown alga Canistrocarpus cervicornis against promastigote forms of Leishmania amazonensis. The antiproliferative assays showed a dose-dependent effect against promastigotes with IC₅₀ values in the range between 20.0 and 80.0µg/mL for crude extracts, 5.0µg/mL for the fraction and 2.0µg/mL for the isolated compound from C. cervicornis. We also investigated targets in the parasite by means of electron microscopy. Ultrastructural alterations were mainly observed in the mitochondrion of parasites treated with the isolated compound. Based on the current study, compounds from C. cervicornis appear to be an alternative for the development of new antiparasitic chemotherapies. However, further in vitro and in vivo studies are necessary to elucidate the mechanism of action of this compound.

Acknowledgements: CNPq, FINEP, PRONEX/Fundação Araucária.

References: [1] Croft, S.L. et al. (2006) Indian J. Med. Res. 123:399–410.

[2] Garcia, D.G. et al. (2009) Phytother. Res., in press.