Estudio químico y evaluación de la actividad citotóxica de metabolitos secundarios provenientes de cianobacterias bentónicas arrecifales del Caribe colombiano

Abstract

Las cianobacterias bentónicas arrecifales son una de las fuentes marinas más prolíficas de compuestos con actividad biológica, dentro de los que destacan: actividad citotóxica contra líneas celulares tumorales, antiparasitaria, neurotóxica, entre otras. En el Caribe colombiano se han observado, cada vez con mayor frecuencia, la presencia de afloramientos de estos microorganismos. Sin embargo, los estudios acerca de su composición química hasta el momento son relativamente pocos. Teniendo en cuenta lo anterior y con el fin de obtener un panorama general acerca de la producción metabólica de las cianobacterias presentes en los afloramientos que se vienen presentando desde el año 2009 en diferentes locaciones del Caribe colombiano, en este trabajo se realizó un estudio metabolómico de 49 extractos de muestras de cianobacterias recolectadas en Islas de rosario, San Andrés y Providencia entre los años 2009 y 2012. Con este estudio se estableció cuáles de las muestras tenían una composición química similar y de esta manera saber cuáles de los extractos podían ser reunidos con el fin de disponer de mayor cantidad de material de partida para un posterior estudio químico. Además fue posible analizar la relación que existe entre las especies presentes en la muestra, año y lugar de recolección con la producción metabólica, dicha información podría contribuir a trabajos de clasificación futuros. Finalmente a partir de este estudio metabolómico junto con algunos ensayos de actividad biológica (Citotoxicidad y antiparasitarios) fue posible generar criterios de selección con los cuales se escogieron dos extractos para continuar con el estudio químico. A partir del extracto de una muestra clasificada como un consorcio de Lyngbya majuscula y Oscillatoria margaritifera se aislaron tres compuestos nuevos de los cuales, uno es 9E, 11Z-1,12-dibromo-4metildodeca-9,11-dien-2-ona (1), un policétido dibromado, que resultó inactivo en todos los ensayos de actividad biológica y dos péptidos denomidados la catalinamida A (2) y catalinamida B (3), compuestos por cinco residuos, cuatro de los cuales corresponden a aminoácidos no proteinogénicos, dentro de los que se encuentra la NMe α-aminoglicina aislada por primera vez de fuentes naturales. Una fracción enriquecida en estos compuestos mostró actividad en los ensayos de citotoxicidad contra la linea celular MFC-7 y contra el parasito Plasmodium falciparum. De un segundo extracto obtenido de una muestra clasificada como Lyngbya sp se identificaron el caylobolido A (4) y el caylobolido B (5) los cuales, en reportes previos habían presentado actividad citotóxica contra varias líneas celulares tumorales. Estos resultados muestran el enorme potencial de las cianobacterias bentónicas arrecifales recolectadas en el Caribe colombiano para producir compuestos con actividad biológica y con estructuras químicamente interesantes, generando información valiosa que permitirá continuar con la exploración de los metabolitos producidos por estos microorganismos con miras a un aprovechamiento sostenible de este recurso.

Abstract. Marine benthic cyanobacteria have been one of the most prolific sources of bioactive compounds, among which cytotoxicity against cancer cell lines, antiphrastic activity and neurotoxicity. Blooms of this microorganism had been observed in Colombian Caribbean Sea more often. However there are only a few studies about their chemical composition. As a result of the mention above and in order to get a panoramic view of the metabolic production of cyanobacteria present in blooms that have been presented since 2009 in different locations in the Colombian Caribbean Sea, in this work, a metabolomic study of 46 cyanobacteria extracts was made, the samples were collected in Islas del Rosario, San Andrés and Providencia between 2009 and 2012. With this study, in was possible to identify which of the samples have similar metabolic production and in this way know if it was possible to mix different extracts from different samples in order to get more starting material for subsequent chemical studies. In addition, the relation between the species present in each sample, the year and the place of recollection with the metabolic production was analyzed and the information here presented could be useful for further studies of classification. Finally with the results obtained in the metabolic study and the biologic activity assays (cytotoxicity and antiphrastic)it was possible to generate criteria for the selection of the extracts to continue with the chemical studies. From extract of the sample classified as Lygnbya spp. caylobolide A and caylobolide B were identified, these two compounds have previous reports of being active against cancer cell lines. Moreover from and extract of a sample classified as Lyngbya majuscula and Oscillatoria margaritifera, three new compounds were identified, the first named XXX is a polyketide dibrominated wich show no activity against none the assays and two peptides named catalinamide A and catalinamide B. A fraction that contains this compounds was tested in the assays showing activity against MFC-7 cell line and the parasite Plasmodium Marine benthic cyanobacteria have been one of the most prolific sources of bioactive compounds, among which cytotoxicity against cancer cell lines, antiphrastic activity and neurotoxicity. Blooms of this microorganism had been observed in Colombian Caribbean Sea more often. However there are only a few studies about their chemical composition. As a result of the mention above and in order to get a panoramic view of the metabolic production of cyanobacteria present in blooms that have been presented since 2009 in different locations in the Colombian Caribbean Sea, in this work, a metabolomic study of 46 cyanobacteria extracts was made, the samples were collected in Islas del Rosario, San Andrés and Providencia between 2009 and 2012. With this study, in was possible to identify which of the samples have similar metabolic production and in this way know if it was possible to mix different extracts from different samples in order to get more starting material for subsequent chemical studies. In addition, the relation between the species present in each sample, the year and the place of recollection with the metabolic production was analyzed and the information here presented could be useful for further studies of classification. Finally with the results obtained in the metabolic study and the biologic activity assays (cytotoxicity and antiphrastic)it was possible to generate criteria for the selection of the extracts to continue with the chemical studies. From extract of the sample classified as Lygnbya spp. caylobolide A and caylobolide B were identified, these two compounds have previous reports of being active against cancer cell lines. Moreover from and extract of a sample classified as Lyngbya majuscula and Oscillatoria margaritifera, three new compounds were identified, the first named XXX is a polyketide dibrominated wich show no activity against none the assays and two peptides named catalinamide A and catalinamide B. A fraction that contains this compounds was tested in the assays showing activity against MFC-7 cell line and the parasite Plasmodium Marine benthic cyanobacteria have been one of the most prolific sources of bioactive compounds, among which cytotoxicity against cancer cell lines, antiphrastic activity and neurotoxicity. Blooms of this microorganism had been observed in Colombian Caribbean Sea more often. However there are only a few studies about their chemical composition. As a result of the mention above and in order to get a panoramic view of the metabolic production of cyanobacteria present in blooms that have been presented since 2009 in different locations in the Colombian Caribbean Sea, in this work, a metabolomic study of 46 cyanobacteria extracts was made, the samples were collected in Islas del Rosario, San Andrés and Providencia between 2009 and 2012. With this study, in was possible to identify which of the samples have similar metabolic production and in this way know if it was possible to mix different extracts from different samples in order to get more starting material for subsequent chemical studies. In addition, the relation between the species present in each sample, the year and the place of recollection with the metabolic production was analyzed and the information here presented could be useful for further studies of classification. Finally with the results obtained in the metabolic study and the biologic activity assays (cytotoxicity and antiphrastic)it was possible to generate criteria for the selection of the extracts to continue with the chemical studies. From extract of the sample classified as Lygnbya spp. caylobolide A and caylobolide B were identified, these two compounds have previous reports of being active against cancer cell lines. Moreover from and extract of a sample classified as Lyngbya majuscula and Oscillatoria margaritifera, three new compounds were identified, the first named XXX is a polyketide dibrominated wich show no activity against none the assays and two peptides named catalinamide A and catalinamide B. A fraction that contains this compounds was tested in the assays showing activity against MFC-7 cell line and the parasite Plasmodium Marine benthic cyanobacteria have been one of the most prolific sources of bioactive compounds, among which cytotoxicity against cancer cell lines, antiphrastic activity and neurotoxicity. Blooms of this microorganism had been observed in Colombian Caribbean Sea more often. However there are only a few studies about their chemical composition. As a result of the mention above and in order to get a panoramic view of the metabolic production of cyanobacteria present in blooms that have been presented since 2009 in different locations in the Colombian Caribbean Sea, in this work, a metabolomic study of 46 cyanobacteria extracts was made, the samples were collected in Islas del Rosario, San Andrés and Providencia between 2009 and 2012. With this study, in was possible to identify which of the samples have similar metabolic production and in this way know if it was possible to mix different extracts from different samples in order to get more starting material for subsequent chemical studies. In addition, the relation between the species present in each sample, the year and the place of recollection with the metabolic production was analyzed and the information here presented could be useful for further studies of classification. Finally with the results obtained in the metabolic study and the biologic activity assays (cytotoxicity and antiphrastic)it was possible to generate criteria for the selection of the extracts to continue with the chemical studies. From extract of the sample classified as Lygnbya spp. caylobolide A and caylobolide B were identified, these two compounds have previous reports of being active against cancer cell lines. Moreover from and extract of a sample classified as Lyngbya majuscula and Oscillatoria margaritifera, three new compounds were identified, the first named XXX is a polyketide dibrominated wich show no activity against none the assays and two peptides named catalinamide A and catalinamide B. A fraction that contains this compounds was tested in the assays showing activity against MFC-7 cell line and the parasite Plasmodium falciparum. With this result it was possible to probe the capacity of marine benthic cyanobacteria to produce bioactive compounds that also have intriguing structures.