RESUMO
A fungal strain of Aspergillus niger was recovered from sediments collected in the Northeast coast of Brazil (Pecém's offshore port terminal). Cultivation in different growth media yielded a new ester furan derivative, 1, along with malformin A1, malformin C, cyclo (trans-4-hydroxy-L-Pro-L-Leu), cyclo (trans-4-hydroxy-L-Pro-L-Phe), cyclo (L-Pro-L-Leu), cyclo (L-Pro-L-Phe), pseurotin D, pseurotin A, chlovalicin, cyclo (L-Pro-L-Tyr) and cyclo (L-Pro-L-Val). Compound 1 was cytotoxic against HCT-116 cell line, showing IC50 = 2.9 µg/mL (CI 95% from 1.8 to 4.7 µg/mL).
Assuntos
Antineoplásicos/farmacologia , Aspergillus niger/química , Antineoplásicos/química , Brasil , Cicloexanonas/isolamento & purificação , Cicloexanonas/farmacologia , Dipeptídeos/isolamento & purificação , Dipeptídeos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Compostos de Epóxi/isolamento & purificação , Compostos de Epóxi/farmacologia , Furanos/química , Sedimentos Geológicos/microbiologia , Células HCT116 , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/farmacologia , Pirrolidinonas/isolamento & purificação , Pirrolidinonas/farmacologiaRESUMO
The cytotoxic activities of extracts (50â µg/ml) from 48 fungal strains, recovered from sediments of Pecém's offshore port terminal (Northeast coast of Brazil), against HCT-116 colon cancer cell lines were investigated. The most promising extract was obtained from strain BRF082, identified as Dichotomomyces cejpii by phylogenetic analyses of partial RPB2 gene sequence. Thus, it was selected for bioassay-guided isolation of the cytotoxic compounds. Large-scale fermentation of BRF082 in potato dextrose broth, followed by chromatographic purification of the bioactive fractions from the liquid medium, yielded gliotoxin (4) and its derivatives acetylgliotoxin G (3), bis(dethio)bis(methylsulfanyl)gliotoxin (1), acetylgliotoxin (5), 6-acetylbis(dethio)bis(methylsulfanyl)gliotoxin (2), besides the quinazolinone alkaloid fiscalin B. All isolated compounds were tested for their cytotoxicities against the tumor cell lines HCT-116, revealing 4 and 3 as the most cytotoxic ones (IC50 0.41 and 1.06â µg/ml, resp.).
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Fungos/química , Sedimentos Geológicos/microbiologia , Antineoplásicos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Brasil , Neoplasias do Colo/tratamento farmacológico , Fungos/genética , Gliotoxina/análogos & derivados , Gliotoxina/química , Gliotoxina/isolamento & purificação , Gliotoxina/farmacologia , Células HCT116 , Humanos , Indóis/química , Indóis/isolamento & purificação , Indóis/farmacologia , Filogenia , Quinazolinas/química , Quinazolinas/isolamento & purificação , Quinazolinas/farmacologiaRESUMO
A fungal strain of Aspergillus sp. (BRF 030) was isolated from the sediments collected in the northeast coast of Brazil, and the cytotoxic activity of its secondary metabolites was investigated against HCT-116 tumour cell line. The cytotoxicity-guided fractionation of the extracts from this fungus cultured in potato-dextrose-sea water for 14 days at room temperature yielded the hetero-spirocyclic γ-lactams pseurotin A (1), pseurotin D (2) and pseurotin FD-838 (7), the alkaloids fumitremorgin C (5), 12,13-dihydroxy fumitremorgin C (6), methylsulochrin (4) and bis(dethio)bis(methylthio)gliotoxin (3). Among them, fumitremorgin C (5) and 12,13-dihydroxy fumitremorgin C (6) were the most active. The cytotoxic activities of the extracts from Aspergillus sp. grown from 7 to 28 days were investigated, and they were associated with the kinetic production of the compounds. The most active extracts (14 and 21 days) were those with the highest relative concentrations of the compounds fumitremorgin C (5) and 12,13-dihydroxy fumitremorgin C (6).