Antimycobacterial Brominated Metabolites from Two Species of Marine Sponges

Abstract

A screening of 500 crude extracts of marine invertebrates against the growth of Mycobacterium tuberculosis H37Rv yielded MeOH extracts of the sponges Aplysina cauliformis and Pachychalina sp. with significant activity. Further bioassay-guided fractionation of both crude extracts led to the isolation of four bromine-containing metabolites. The known (+)-fistularin-3 (1) and 11-deoxyfistularin-3 (2), and the new compound 2-(3-amino-2,4-dibromo-6-hydroxyphenyl)acetic acid (3) were isolated from the sponge A. cauliformis, while the new bromotyrosine-derived 3-(3,5-dibromo-4-methoxyphenyl)-2-methoxy- N-methylpropan-1-ammonium (4) was isolated from Pachychalina sp. Compound 4 exhibited weak antimycobacterial activity while compounds 1-3 displayed activity against Mycobacterium tuberculosis H37Rv, with MICs of 7.1, 7.3 and 49 microM, respectively. Compounds 1 and 2 also exhibited low cytotoxicity against J744 macrophages, indicating that both 1 and 2 are interesting leads for the development of new anti-tuberculosis agents.

Antibiotic, cytotoxic and enzyme inhibitory activity of crude extracts from Brazilian marine invertebrates

“…The subsequent chemical investigation of crude extracts from marine invertebrates screened in this investigation led to the isolation of several biologically active compounds Gray et al, 2006;Torres et al, 2002b;Saeki et al, 2002;Oliveira et al, 2006a;Oliveira et al, 2006b;Kossuga et al, 2004;Kossuga et al, 2007). Continuing studies of secondary metabolites of these and other softbodied marine invertebrates will certainly yield several new bioactive molecules, which may be envisaged as new leads in drug-discovery programs .…”

“…BA99-26, later identifi ed as A. cauliformis, displayed antimycobacterial activity against M. tuberculosis. The active compounds were isolated and identifi ed as the known (+)-fi stularin-3 and 11-desoxyfi stularin-3 (Oliveira et al, 2006a). Currently the Aplysina spp.…”

Metabólitos secundários das esponjas Aplysina fistularis e Dysidea sp. e atividade antituberculose da 11-cetofistularina-3

“…O extrato metanólico de A. fistularis foi submetido a várias separações cromatográficas (ver Parte Experimental), resultando na obtenção dos derivados da dibromotirosina aeroplisinina-2 (4), 15 2-(3,5-dibromo-4-metoxifenil)-N,N,N-trimetiletanamônio (5), 16 o ácido 7,9-dibromo-10-hidroxi-8-metoxi-1-oxa-2-azaspiro [4.5] deca-2,6,8-trieno-3-carboxílico (6), 17 bem como o éster metílico deste último (7), 18 a 11-oxoaerotionina (8), 19 a aerotionina (9), 20 a 11-ceto-12-hidroxiaerotionina (10), 21 a 11-cetofistularina-3 (11) 22 e a fistularina-3 (12). 23 Todos os derivados da dibromotirosina isolados de A. fistularis coletada na Baía de Todos os Santos foram identificados pela análise de seus dados espectroscópicos e por comparação com dados da literatura, cujas referências para comparação são indicadas para os compostos 4-12 na seção experimental.…”

“…3 Sendo assim, é evidente a importância de produtos do metabolismo secundário na descoberta e desenvolvimento de medicamentos para o tratamento da tuberculose. [4][5][6][7][8][9][10] A prospecção de extratos de invertebrados marinhos da costa do Brasil com atividade antituberculose 11 levou-nos à descoberta de derivados da dibromotirosina, 12 bem como de alcaloides alquilpiridínicos 13 e alquilpiperidínico 14 ativos contra M. tuberculosis H37Rv. A continuidade deste programa nos levou a investigar os extratos de duas esponjas marinhas, Aplysina fistularis e Dysidea sp., das quais os extratos metanólicos apresentaram atividade antituberculose contra M. tuberculosis H37Rv.…”

A multi-screening approach for marine-derived fungal metabolites and the isolation of cyclodepsipeptides from Beauveria felina

“…Considering that the occurrence of fungi in the marine environment was first reported late in the nineteenth century [1][2][3][4] and that the oceans cover more than 70% of the Earth's surface, the number of species of marine fungi which have been described is surprisingly much smaller than terrestrial species. This is because not only is marine mycology a recent science, but also because it seems to be inherently more difficult to access artificial media and growth conditions to isolate and to grow both new facultative and new obligate marine fungi.…”