The antibiotic-resistant bacteria seriously threaten public heath. Scientists of both public and private sectors are devoted to develop new drugs to overcome this problem. Marine species are highly diversity and have been shown to be a potential sources to find efficient compounds. The medicine application of the natural products from ocean increases in last decade. The purpose of the project was to isolate antibiotic-producers from sea-bottom mud. Three filament microorganisms from marine environment, Acremonium altematum T1-1, Aspergillus ochraceus N7 and Nocardiopsis dassonvillei F5, can produce bioactivity compounds. All compounds purified using silica chromatographic separation from culture extraction and determination of their structure by NMR spectrum and X-ray diffraction pattern for crystals. A. altematum T1-1 produced 5,6-dihydropenicillic acid (DHPA), A. ochraceus N7 produced penicillic acid (PA), and N. dassonvillei F5 produced iodinin. The structures of DHPA and PA were identified as derivatives of five-member lactone, and iodinin is a derivative compound of phenazine. The optimal growth of DHPA -producer A. altematum T1-1 was in 6% salinity at 30¢J and best DHPA production was in 0% salinity at 25¢J. The optimal growth of PA-producer A. ochraceus N7 was in 6% salinity at 25¢J, and best PA production conditions was below 3% salinity at 25 ¢J. The optimal growth of iodinin-producer N. dassonvillei F5 was in 6% salinity at 30¢J and best iodinin production condition was 1-3% salinity at 25¢J. Only PA has highly inhibited of B. cereus at the MIC of 75 mg/ml. The PA had cytotoxicity against cancer cell lines of P-388, HT-29 and A549 while iodinin inhibited P-388 and A549. The ED50 on the swimming ability of rotifer was 1.03 and 2.5 mg/ml for PA and DHPA, respectively. It revealed that the growth of these two mold can occur in regular marine environment and produce toxin to kill rotifer. The growth of N. dassonvilleiand F5 and iodinin caused the death and virus-invasion of shrimp.

Este trabalho descreve o estudo de bioprospecÃÃo de metabÃlitos secundÃrios citotÃxicos do PecÃm-CE. Inicialmente, foi realizado o estudo cinÃtico da produÃÃo de metabÃlitos secundÃrios por P. lilacinus cultivado no meio de batata-dextrose (BD) durante 7, 14 21 e 28 dias. AtravÃs da anÃlise cromatogrÃfica dos extratos, bem como dos resultados de atividade citotÃxica dos mesmos, frente à linhagem de cÃlula tumoral HCT -116 (cÃncer de cÃlon), foi possÃvel selecionar o extrato oriundo do crescimento do fungo por 14 dias (inibiÃÃo de crescimento:85,7 %) como o mais citotÃxico. O fracionamento bioguiado do extrato orgÃnico do fungo cultivado por 14 dias em grande escala levou ao isolamento dos esterÃides wortimanina e 11-deacetoxiwortimanina, ambos inÃditos no gÃnero Paecilomyces . Os metabÃlitos secundÃrios foram isolados at ravÃs de mÃtodos cromatogrÃficos usuais e CLAE (Cromatografia lÃquida de alta eficiÃncia). A caracterizaÃÃo estrutural foi realizada atravÃs do uso de mÃtodos espectromÃtricos, especialmente espectrometria de massas, ressonÃncia magnÃtica nuclear (1H e 13C) e infravermelho, alÃm de comparaÃÃo de dados da literatura. TambÃm foi realizado um estudo de desreplicaÃÃo do extrato, o qual sugeriu a presenÃa dos compostos ciclosinefungina, estatana A, virescenosideo -D, (+)-esclerotiorina, 2'-Amino-2'-deoxiguanosina , fumaramidimicina e deoxinivalenol, todos inÃditos no gÃnero Paecilomyces produzidos por Paecilomyces lilacinus (cepa BRF053) recuperado de sedimentos da praia. / The bioprospection of cytotoxic secondary metabolites produced by Paecilomyces lilacinus(fungal strain BRF053) recovered from sediments collected at PecÃm beach, Cearà state, was investigated. First, the production of compounds by the fungal strain was performed by culturing the microorganism in potato-dextrose broth (PDB) for 7,14,21 and 28 days. Both HPLC analysis and cytotoxic activity(tumor cell line HCT-116) of the extracts from each period of culture revealed 1 4 days as the optimum time for producing cytotoxic compounds (growth inhibition 85.7 %). Bioguided fractionation of the organic extract from the fungus cultured in large scale under the same conditions (14 days) allowed the isolation of the steroids wortimann in and 11-deacetox ywortiman n in, both new compounds in Paecilomyces. These compounds were isolated by chromatography column and HPLC, and their structures were elucidated by spectrometric methods (HRMS, 1H, 13C NMR, and IR) besides comparison with literature data. Dereplication of the extract by LC -MS suggested the presence of cyclosinefungin, stanna A, virescenoside-D, (+)-esclerotiorin, 2'-Amino-2'-deoxiguanosine, fumaramidimicin e deoxy nivalenol, all of the new compounds in Paecilomyces.