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Bioprospecting deep-sea marine animal lipids from Azores for therapeutic applications
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Abstract(s)
A região dos Açores apresenta uma grande diversidade de comunidades faunísticas em ecossistemas marinhos de profundidade, com numa grande variedade de "hotspots" no fundo do mar, tais como montes submarinos, encostas das ilhas e fontes hidrotermais. No entanto, apesar desta enorme biodiversidade, os seus invertebrados marinhos de profundidade nunca foram bio prospectados enquanto produtos naturais marinhos funcionais. Esta tese teve como objectivo fazê-lo.
Foram extraídos lípidos de dezanove espécies animais, num total de trinta e seis extractos brutos, subsequentemente testados in vitro como antibacterianos, antimaláricos e anticancerígenos. Da diversidade de animais de profundidade que incluiu corais, esponjas, ouriços e invertebrados das fontes hidrotermais, os resultados revelaram que os extractos apresentam actividade para todos os ensaios biológicos testados, com as esponjas a apresentarem-se como os animais mais úteis como fonte de compostos naturais marinhos anticancerígenos e os corais de água fria, como antimaláricos.
Foi usada uma estratégia de fracionamento guiado pela bioactividade, nos extractos dos animais mais activos: as mega-esponjas Petrosia sp. E Leiodermatium sp.. Os esteróis (Petrosterol, Sitosterol e 23, 24-Dihydrocalysterol) foram identificados nas fracções de Petrosia sp. Mais anticancerígenas mas devido a perca de actividade durante a separação dos compostos, não foi possível confirmá-los como principais anticancerígenos presentes. O estudo com a esponja Leiodermatium sp. resultou no isolamento de uma mistura complexa de compostos, demonstrando um potente efeito anticancerígeno (IC75=0,08 μg/ml). Os compostos foram identificados como pertencentes a uma mesma família de macrólidos e foram denominados "azorelides". Foi possível isolar os compostos azorelide A e azorelide B mas a esteroquímica absoluta de ambas as moléculas não foi determinada devido às suas escassas quantidades (1,1 mg de azorelide A/kg e 0,47 mg de azorelide B/kg de esponja Leiodermatium seca).
ABSTRACT: Azores region presents a great diversity of deep-sea ecosystems with faunal communities in a variety of benthic hotspots, as seamounts, islands slopes and hydrothermal vents. Despite its high biodiversity, these deep-sea invertebrates were never bio prospected in regard to their natural products. This thesis aims to do so. Lipids were extracted from nineteen animal species and a total of thirty-six crude extracts were tested in vitro as potential antibacterial, antimalarial and anticancer activities. From a deep-sea diversity of corals, sponges, seaurchins and hydrothermal vents invertebrates, results showed that extracts were active for all tested bioassays, with sponges presenting the best outcomes as anticancer and corals as antimalarial natural product sources. A bioactivity-guided fractionation strategy was used in the most active animal extracts: the mega sponges Petrosia sp. and Leiodermatium. Sterols (Petrosterol, Sitosterol and 23, 24- Dihydrocalysterol) were identified in the most active anticancer fraction from Petrosia sp. but, due to activity lost during compounds isolation, it was not possible to confirm these as the main anticancer compounds present. Study with Leiodermatium sponge extracts lead to isolation of a complex mixture of compounds, showing potent anticancer activities (IC75=0.08 μg/ml). Compounds were identified as belonging to the same macrolide family and were named "azorelides". It was possible to isolate azorelide A and azorelide B, but their absolute stereochemistry was not achieved due to amount scarcity (1.1 mg of azorelide A/kg and 0.47 mg of azorelide B/kg of dry Leiodermatium sponge).
ABSTRACT: Azores region presents a great diversity of deep-sea ecosystems with faunal communities in a variety of benthic hotspots, as seamounts, islands slopes and hydrothermal vents. Despite its high biodiversity, these deep-sea invertebrates were never bio prospected in regard to their natural products. This thesis aims to do so. Lipids were extracted from nineteen animal species and a total of thirty-six crude extracts were tested in vitro as potential antibacterial, antimalarial and anticancer activities. From a deep-sea diversity of corals, sponges, seaurchins and hydrothermal vents invertebrates, results showed that extracts were active for all tested bioassays, with sponges presenting the best outcomes as anticancer and corals as antimalarial natural product sources. A bioactivity-guided fractionation strategy was used in the most active animal extracts: the mega sponges Petrosia sp. and Leiodermatium. Sterols (Petrosterol, Sitosterol and 23, 24- Dihydrocalysterol) were identified in the most active anticancer fraction from Petrosia sp. but, due to activity lost during compounds isolation, it was not possible to confirm these as the main anticancer compounds present. Study with Leiodermatium sponge extracts lead to isolation of a complex mixture of compounds, showing potent anticancer activities (IC75=0.08 μg/ml). Compounds were identified as belonging to the same macrolide family and were named "azorelides". It was possible to isolate azorelide A and azorelide B, but their absolute stereochemistry was not achieved due to amount scarcity (1.1 mg of azorelide A/kg and 0.47 mg of azorelide B/kg of dry Leiodermatium sponge).
Description
Tese de Doutoramento, Ciências do Mar, especialidade de Recursos Marinhos, 27 de Novembro de 2015, Universidade dos Açores.
Keywords
Biodiversidade Marinha Bioquímica Biologia Molecular Espécies Marinhas (Potencial Farmacológico) Fontes Hidrotermais Marinhas Açores Deep-Sea Invertebrates Hydrothermal Vents Marine Lipids
Citation
Lino, Sílvia Patrícia Pena. "Bioprospecting deep-sea marine animal lipids from Azores for therapeutic applications". 2015. 154 p.. (Tese de Doutoramento em Ciências do Mar, especialidade de Recursos Marinhos). Horta: Universidade dos Açores, 2015. [Consult. Dia Mês Ano]. Disponível em www:<http://hdl.handle.net/10400.3/4073>.