Vinsamlegast notið þetta auðkenni þegar þið vitnið til verksins eða tengið í það: http://hdl.handle.net/1946/20871
Introduction: In the year 2013,9 million people were infected by Mycobacterium tuberculosis, one of the reason for the high number of infected is drug resistance against antibiotics. Thus, it is an essential mission to develop new treatments against it. Natural products have been important source for development of new antimicrobial. Marine-derived fungi are interesting organisms in the field of natural products drug development. From the year 2002-2010, over 800 new metabolites from marine-derived fungi were published. Many of these metabolites have been shown to possess various bioactiviy e.g. anticancer and antimicrobial activities. When looking for new drug leads, great biodiversity and extreme environment are the most interesting places to search for secondary metabolites. Iceland has an unique geology and geographical position, surrounded by cold water masses from the Arctic Ocean and warmer sea of the Gulf Stream from the south. All this makes it an interesting environment for biopropecting and drug discovery. In addition, Iceland and the extensive waters around it are largely unexplored with respect to biologically active secondary metabolites.
Aim: to isolate and structurally elucidate secondary metabolites from marine- and fresh water-derived fungal strains collected in Icelandic waters and screen fractions for antimycobacterial activity in vitro.
Results: First the fungal strains were cultivated on agar plates, followed by liquid culture. Secondary metabolites were extracted with organic solvents and resin and the crude extracts obtained were fractionated into four fractions with different polarities. Several fractions showed inhibition against antimycobacterial effects in vitro. Five fractions were selected for further isolation. The chemical profiles of the fractions were obtained by liquid chromatography (LC) coupled to diode array detector (DAD), evaporating light scattering detector (ELSD) and mass spectrometer (MS) and with nuclear magnetic resonance spectroscopy (NMR). The chromatographs and spectra of the fractions were compared with those of known compounds in both in-house and online databases and further studies were done on those that were considered to contain new compounds. Fraction FK003-F2 appeared to contain a new compound but it turned out to be a known compound, maximiscin. Maximiscin is a mixture of rapidly interconverting atropisomers, a polyketide-shikimate-NRPS-hybrid compound that has previously been shown to have in vitro cytotoxic activity and in vivo antitumor activity. Another fraction, FK001-RF3 obtained after a regrown of the strain, appeared to contain three new compounds from the initial data. However, structure elucidation is still in progress and further NMR and HRMS data are needed to determine the structures in detail. The next step is to test antimycobacterial activity of the pure compounds isolated in this project.
Conclusion: Marine-derived fungi collected in Icelandic waters produce variety of biologically active secondary metabolites. Several fractions from these strains inhibit Mycobacterium tuberculosis in in vitro assays. In this study, the previously known anticancer compound maximiscin was isolated from one strain (FK003) and a potential new class of chlorinated compounds were isolated from another strain (FK001). Structure elucidation of these “new” compounds is in process.
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