Marine algae extracts as  source of natural antileishmanial compounds

Sousa, Carolina Amaral Frade Bruno de

http://hdl.handle.net/10400.1/10778

Use this identifier to reference this record.

Name:	Description:	Size:	Format:
Tese PhD - Carolina Bruno de Sousa.pdf		11.32 MB	Adobe PDF	Download

Send Feedback

Authors

Sousa, Carolina Amaral Frade Bruno de

Advisor(s)

Varela, J.

Campino, Lenea

Abstract(s)

This thesis aimed to identify Cystoseira macroalgae compounds displaying antileishmanial activity. Concerning the need to ensure the identification of the samples used for the drug screening, a second aim was determined to evaluate the usefulness of mitochondrial markers for identification of Cystoseira. A comprehensive review showed that marine algae, and in particular Cystoseira, are important sources of bioactive compounds, which can be used as antiparasitic agents (Chapter I and II). This work revealed that these algae contains compounds with antileishmanial activity. Forty five extracts from 15 species was submitted to bio-guided fractionation and its activity against L. infantum promastigotes and their cytotoxicity evaluated. Among the studied algae, Cystoseira extracts (C. baccata, C. barbata, C. nodicaulis and C. tamariscifolia) displayed the most interesting activities against this parasite (Chapter III). C. baccata baccatabaccata hexane extract was hexane extract was hexane extract was hexane extract was hexane extract was hexane extract was hexane extract was hexane extract was hexane extract was hexane extract was hexane extract was hexane extract was further investigated, to the isolation of two active active active active active meroterpenoids meroterpenoids meroterpenoids meroterpenoids : the the (3R)- and (3S)-tetraprenyltoluquinone with an unknown structure, and the (3R)- and (3S)-tetraprenyltoluquinol previously isolated and active against Leishmania intracellular amastigote forms. Promastigote ultrastructural alterations, DNA fragmentation and mitochondrial potential variations suggest that the mechanism of action of these compounds interfere with the mitochondrial metabolism (Chapters IV). Moreover, the investigation of the chemical composition of the Cystoseira crude extracts showed that these algae contain fatty acids, triacylglycerols, carotenoids, steroids and meroterpenoids (Chapter III). This characterization complement published data, suggesting that these compounds might also be involved in the antileishmanial activity here unravelled (Chapter II). Concerning the identification of Cystoseira, samples from twenty-two Cystoseira species were analysed generating 135 new sequences of three mitochondrial regions (COI, 23S and mt-spacer). This work demonstrated that these three markers are suitable to distinguish these species. The results allowed for the correct identification of Cystoseira samples used for drug screening, encouraging the study of taxonomy and evolutionary elucidation of these brown algae using genetic tools (Chapter V).