Estudo químico e biológico das esponjas Agelas e Agelas dispar do Nordeste do Brasil

O gênero de esponjas marinhas Agelas sp. é conhecido como fonte de alcaloides bromados dos tipos pirrol e imidazol, além de terpenoides, esteróis e ácidos graxos, metabólitos que estão relacionados com muitas atividades biológicas. Neste trabalho, amostras fracionadas a partir dos extratos metanólicos de Agelas coletadas na costa nordeste brasileira, foram analisadas em sistemas CLAE-EM, nos modos positivo e negativo, e caracterizados os metabólitos 4,5-dibromopirrol-2-carboxamida (1) ácido 4,5-dibromopirrol-2-carboxílico (2), bromopirrol-2-carboxamida (3) ácido bromopirrol-2-carboxílico (4), éster metílico da longamida B (5), hanishina (6), 9,10-di-hidrokeramadina (7), mukanadina E (8), agelanesina (9), dibromosceptrina (10), dispacamida C (11), dispacamida A (12), agesamida (13), éter metílico da dibromoagelaspongina (14), agelanina b (15), longamida (16), metil-himenidina (17), agelanesina c (18), manzacidina A (19), bromohimenialdisina (20), oroidina (21), agelasidina A (22), 5-hidroxilisina (23), himenidina (24), mukanadina A (25), clatramida A (26) e longamida (27). Também foram identificados ácidos graxos como os ácidos pentadecanoico, margárico, palmítico e esteárico, além do nonadeceno, docosanol, tetracosanol, pentacosanol, heptacosanol, ácido behênico e esqualeno, obtidos a partir do fracionamento de extratos lipídicos e analisados através de CG-EM. Frações resultantes de partição do extrato bruto de A. dispar e Agelas foram testadas em ensaios microbiológicos e demonstraram moderada a alta ação antibacteriana e antifúngica, contra organismos como Staphylococcus aureus, S. epidermidis, S. hominis, Enterococcus faecalis, E. faecium, Pseudomonas aeruginosa, Escherichia Coli, Salmonella enteriditis, Klebsiella pneumoniae, Candida albicans, C. cruzei e C. tropicalis, assim como fraca ação antioxidante. Foram isolados o esterol β-sitosterol e o alcaloide 4,5-dibromopirrol-2-carboxamida, sendo que o último demonstrou potente atividade antibacteriana e antifúngica, com o melhor valor de CIM= 0,25 µg/mL e CBM/CFM=0,25 µg/mL. Foi realizado o levantamento bibliográfico de dados espectrométricos de substâncias de Agelas na literatura. O fracionamento e identificação dos metabólitos foram realizados através de técnicas cromatográficas clássicas, CG-EM, CLAE-EM e RMN1H e RMN13C, uni e bidimensionais. Sponges from the genus Agelas sp. are known as source of brominated pyrrole and imidazole alkaloids, as well as terpenoids, sterols and fatty acids, metabolites that are associated with various biological activities. In this work, fractionated samples from Agelas sp. and Agelas dispar methanolic extracts, collected on the northeast coast of Brazil, were analyzed in HPLC-MS systems, and the following metabolites were characterized through positive and negative mode MS: 4,5-dibromo-1H-pyrrole-2-carboxamide (1), 4,5- dibromopyrrole-2-carboxylic acid (2), bromopyrrole-2-carboxamide (3) bromopyrrole-2- carboxylic acid (4), longamide B methyl esther (5), hanishin (6), 9,10-di-hydrokeramadin (7), mukanadin E (8), agelanesin (9), dibromosceptrin (10), dispacamide C (11), dispacamide A (12), agesamide (13), dibromoagelaspongin methyl ether (14), agelanin b (15), longamide (16), methyl-hymenidin (17), agelanesin c (18), manzacidine a (19), bromohymenialsidin (20), oroidin (21), agelasidine a (22), 5-hidroxilisine (23), hymenidin (24), mukanadine A (25), clathramide A (26) and longamide (27). Also were identified fatty acids, such as pentadecanoic, margaric, palmitic and stearic, as well as nonadecene, docosanol, tetracosanol, pentacosanol, heptacosanol, behenic acid and squalene, obtained from fractionation and GCMS analysis of lipid extracts. Fractions resulting from the partition of A. dispar and Agelas sp. crude and semi-crude extract were tested in microbiological assays and demonstrated moderate to high antibacterial action and antifungal activities, against organisms such as Staphylococcus aureus, S. epidermidis, S. hominis, Enterococcus faecalis, E. faecium, Pseudomonas aeruginosa, Escherichia Coli, Salmonella enteriditis, Klebsiella pneumoniae, Candida albicans, C. cruzei and C. tropicalis, beside poor antioxidant activity. The sterol βsitosterol and the alkaloid 4,5-dibromopyrrole-2-carboxamide were isolated, and the latter showed potent antibacterial and antifungal activity in the assay performed, with the best MIC = 0.25 μg/ mL and MBC/ MFC = 0.25 μg/ mL. Collection of spectrometric data from Agelas sp. substances available on literature was performed. Fractioning, characterization and identification of metabolites was achieved through classical chromatographic techniques, GCMS, HPLC-MS, HPLC-MS-MS and uni and bidimensional 1H NMR and 13C NMRSponges from the genus Agelas sp. are known as source of brominated pyrrole and imidazole alkaloids, as well as terpenoids, sterols and fatty acids, metabolites that are associated with various biological activities. In this work, fractionated samples from Agelas sp. and Agelas dispar methanolic extracts, collected on the northeast coast of Brazil, were analyzed in HPLC-MS systems, and the following metabolites were characterized through positive and negative mode MS: 4,5-dibromo-1H-pyrrole-2-carboxamide (1), 4,5- dibromopyrrole-2-carboxylic acid (2), bromopyrrole-2-carboxamide (3) bromopyrrole-2- carboxylic acid (4), longamide B methyl esther (5), hanishin (6), 9,10-di-hydrokeramadin (7), mukanadin E (8), agelanesin (9), dibromosceptrin (10), dispacamide C (11), dispacamide A (12), agesamide (13), dibromoagelaspongin methyl ether (14), agelanin b (15), longamide (16), methyl-hymenidin (17), agelanesin c (18), manzacidine a (19), bromohymenialsidin (20), oroidin (21), agelasidine a (22), 5-hidroxilisine (23), hymenidin (24), mukanadine A (25), clathramide A (26) and longamide (27). Also were identified fatty acids, such as pentadecanoic, margaric, palmitic and stearic, as well as nonadecene, docosanol, tetracosanol, pentacosanol, heptacosanol, behenic acid and squalene, obtained from fractionation and GCMS analysis of lipid extracts. Fractions resulting from the partition of A. dispar and Agelas sp. crude and semi-crude extract were tested in microbiological assays and demonstrated moderate to high antibacterial action and antifungal activities, against organisms such as Staphylococcus aureus, S. epidermidis, S. hominis, Enterococcus faecalis, E. faecium, Pseudomonas aeruginosa, Escherichia Coli, Salmonella enteriditis, Klebsiella pneumoniae, Candida albicans, C. cruzei and C. tropicalis, beside poor antioxidant activity. The sterol βsitosterol and the alkaloid 4,5-dibromopyrrole-2-carboxamide were isolated, and the latter showed potent antibacterial and antifungal activity in the assay performed, with the best MIC = 0.25 μg/ mL and MBC/ MFC = 0.25 μg/ mL. Collection of spectrometric data from Agelas sp. substances available on literature was performed. Fractioning, characterization and identification of metabolites was achieved through classical chromatographic techniques, GCMS, HPLC-MS, HPLC-MS-MS and uni and bidimensional 1H NMR and 13C NMR.