Micro-organisms Marine Producers Biologically Active Secondary Metabolites

Este trabalho descreve o estudo quÃmico e biolÃgico dos extratos das bactÃrias marinhas Pseudoalteromonas sp., Micromonospora sp., Streptomyces sp. e Kocuria sp., visando o isolamento e a elucidaÃÃo estrutural de novos constituintes bioativos. A investigaÃÃo quÃmica realizada com a bactÃria Pseudoalteromonas sp. resultou no isolamento de um pigmento vermelho identificado como prodigiosina e de dois Ãcidos biliares conhecidos como Ãcido desoxicÃlico e Ãcido cÃlico. A prodigiosina foi testada frente a quatro linhagens de cÃlulas tumorais e apresentou valores de IC50 semelhantes ao padrÃo positivo. O estudo quÃmico de Micromonospora sp. resultou no isolamento de quatro novas antraciclinonas: 4,6,11-triidroxi-9-propriltetraceno-5,12-diona; 4-metoxi-9-propiltetraceno-6,11-diona; 7,8,9,10-tetraidro-9-hidroxi-4-metoxi-9-propiltetra-ceno-6,11-diona e 10β-metoxicarbonil-7,8,9,10-tetraidro-4,6,7α,9α,11âpentaidroxiâ9âpropil-tetraceno-5,12-diona. Esses compostos foram avaliados quanto a sua atividade anti-tumoral frente a linhagem celular HCT-8, dois dos quais mostraram citotoxidade moderada com valores de IC50 de 12,74 e 6,18 M. O estudo da bactÃria Streptomyces sp. possibilitou o isolamento de uma ditiolpirrolidina cuja estrutura foi estabelecida como 5-oxo-6-(N-metilformamida)-4,5- diidro-1,2-ditiol[4,3-b]pirrol. Esse metabÃlito teve sua atividade citotÃxica testada frente a seis linhagens celulares tumorais, mostrando forte atividade com IC50 de 1,66, 1,05 e 1,52 ÂM para as linhagens de prÃstata metastÃtica, carcinoma de ovÃrio e glioblastoma, respectivamente. O estudo de Kocuria sp. resultou no isolamento de um novo peptÃdeo denominado como kocurina. Esse composto teve sua atividade antimicrobiana testada frente a vÃrias bactÃrias e fungos patogÃnicos, incluindo cepas de Staphylococcus aureus resistentes a meticilina (MRSA) e cepas de Staphylococcus aureus resistentes a tiazomicina. Kocurina inibiu fortemente o crescimento de MRSA MB5393 com valores de CIM de 0,25Âg/mL, alÃm de exibir atividade antibacteriana contra as bactÃrias Bacillus subtilis e Enterococcus faecium. As estruturas de todos os compostos isolados neste trabalho foram determinadas empregando mÃtodos espectroscÃpicos tais como RMN 1H e 13C (1D e 2D), espectrometria de massas e infravermelho.This work describe the chemical and biological investigation of the extracts from the marine bacterias Pseudoalteromonas sp., Micromonospora sp., Streptomyces sp. and Kocuria sp., aiming the isolation and structural elucidation of new bioactive constituents. The chemical investigation carried out with the bacteria Pseudoalteromonas sp. lead to the isolation a red pigment identified as prodigiosin and two bile acids derivatives known as deoxycholic acid and cholic acid. The prodigiosin was evaluated against four tumor cell lines showing IC50 values similar to the positive control doxorubicin. The chemical study of Micromonospora sp. Resulted in the isolation of four new anthracyclinones designed as 4,6,11-trihydroxy-9-propryltetracene-5,12-dione; 4-methoxy-9-propyltetracene-6,11-dione; 7,8,9,10 - tetrahydro-9-hydroxy-4-methoxy-9-propiltetra-cene-6,11-dione and 10β-Carbomethoxy-7,8,9,10-tetrahydro-4,6,7α,9α,11-pentahydroxy-9-propyltetracene-5,12-dione . The cytotoxic potential of these compounds were evaluated against HCT-8cell line, two of which showed moderate cytotoxicity with IC50 values of 12.74 and 6.18 M, respectively. From Streptomyces sp. strain was isolated a ditiolpyrrolidin, established as 5-oxo-6-(N-methylformamide) -4,5 - dihydro-1,2-dithiol [4,3-b] pyrrole. This secondary metabolite was tested against six tumor cell lines, shown IC50 values of 1.66, 1.05 and 1.52 mM for the metastatic prostate lines, ovarium carcinoma and glioblastoma, respectively. The study of Kocuria sp. lead to the isolation of a new peptide, which was designed as kocurin. This compound was subjected to the tested its antimicrobial assays against several pathogens bacteria and fungal including Staphylococcus aureus strains methicillin resistant (MRSA) and Staphylococcus aureus strains tiazomicin resistant. Kocurin was strongly active against MRSA MB5393 exhibiting a MIC of 0,25Âg/mL, moreover showed antibacterial activity against Bacillus subtilis and Enterococcus faecium. The structures of all isolated compounds in this work were stabilized employing spectroscopic methods such as 1H and 13C NMR (1D and 2D), mass spectrometry and infrared