Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata

Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata

Author de Sousa, Carolina Bruno Google Scholar
Gangadhar, Katkam N. Google Scholar
Morais, Thiago R. Autor UNIFESP Google Scholar
Conserva, Geanne A. A. Autor UNIFESP Google Scholar
Vizetto-Duarte, Catarina Google Scholar
Pereira, Hugo Google Scholar
Laurenti, Marcia D. Google Scholar
Campino, Lenea Google Scholar
Levy, Debora Google Scholar
Uemi, Miriam Autor UNIFESP Google Scholar
Barreira, Luisa Google Scholar
Custodio, Luisa Google Scholar
Passero, Luiz Felipe D. Google Scholar
Lago, Joao Henrique G. Autor UNIFESP Google Scholar
Varela, Joao Google Scholar
Abstract The development of novel drugs for the treatment of leishmaniases continues to be crucial to overcome the severe impacts of these diseases on human and animal health. Several bioactivities have been described in extracts from macroalgae belonging to the Cystoseira genus. However, none of the studies has reported the chemical compounds responsible for the antileishmanial activity observed upon incubation of the parasite with the aforementioned extracts. Thus, this work aimed to isolate and characterize the molecules present in a hexane extract of Cystoseira baccata that was found to be bioactive against Leishmania infantum in a previous screening effort. A bioactivity-guided fractionation of the C. baccata extract was carried out and the inhibitory potential of the isolated compounds was evaluated via the MIT assay against promastigotes and murine macrophages as well as direct counting against intracellular amastigotes. Moreover, the promastigote ultrastructure, DNA fragmentation and changes in the mitochondrial potential were assessed to unravel their mechanism of action. In this process, two antileishmanial meroditerpenoids, (3R)- and (3S)-tetraprenyltoluquinol (1a/1b) and (3R)- and (3S)-tetraprenyltoluquinone (2a/2b), were isolated. Compounds 1 and 2 inhibited the growth of the L. infantum promastigotes (IC50 = 44.9 +/- 4.3 and 94.4 +/- 10.1 mu M, respectively), inducing cytoplasmic vacuolization and the presence of coiled multilamellar structures in mitochondria as well as an intense disruption of the mitochondrial membrane potential. Compound 1 decreased the intracellular infection index (IC50 = 25.0 +/- 4.1 mu M), while compound 2 eliminated 50% of the intracellular amastigotes at a concentration > 88.0 mu M. This work identified compound 2 as a novel metabolite and compound 1 as a biochemical isolated from Cystoseira algae displaying antileishmanial activity. Compound 1 can thus be an interesting scaffold for the development of novel chemotherapeutic molecules for canine and human visceral leishmaniases studies. This work reinforces the evidence of the marine environment as source of novel molecules. (C) 2017 Elsevier Inc. All rights reserved.
Keywords Leishmania infantum
Macroalgae
Cystoseira baccata
Meroterpenoids
Tetraprenyltoluquinol
Tetraprenyltoluquinone
xmlui.dri2xhtml.METS-1.0.item-coverage San Diego
Language English
Sponsor Portuguese FCT
FAPESP
CNPq
FCT doctoral grants
FCT Investigator Programme
Grant number Portuguese FCT: PTDC/MAR/103957/2008
Portuguese FCT: CCMAR/Multi/04326/2013
FAPESP: 2013/16297-2
FAPESP: 2015/11936-2
CNPq: 470853/2012-3
FCT doctoral grants: SFRH/BD/78062/2011
FCT doctoral grants: SFRH/BD/81425/2011
FCT doctoral grants: SFRH/BD/105541/2014
FCT doctoral grants: SFRH/BPD/81882/2011
FCT Investigator Programme: IF/00049/2012
Date 2017
Published in Experimental Parasitology. San Diego, v. 174, p. 1-9, 2017.
ISSN 0014-4894 (Sherpa/Romeo, impact factor)
Publisher Academic Press Inc Elsevier Science
Extent 1-9
Origin http://dx.doi.org/10.1016/j.exppara.2017.01.002
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000396381600001
URI https://repositorio.unifesp.br/handle/11600/55008

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