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Browsing by Subject "purpurealidiini I"

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  • Flemmich, Paul (2015)
    There are dozens of bromotyrosine alkaloids extracted from the marine sponge Pseudoceratina purpurea. Bromotyrosines have for example antibacterial, antiviral and antitumor activity in vitro and therefore bromotyrosines are potential drug lead molecules. By far, bromotyrosines have been extracted from different marine sponges of the Verongida order for the use in biological activity research. Collecting marine sponges by scuba diving is neither fast nor ecological and therefore finding an effective synthesis strategy is vital so that the research could continue. One new bromotyrosine, purpurealidin I, was found from the marine sponge Pseudoceratina purpurea in the four year (2010-2014) Marex-project. The aim of this thesis was to synthesize the compound purpurealidin I and its derivatives. Synthesized compounds were tested against hepatitis C and chikungunya viruses. It is important to find new potent drug molecules, because approximately 350 000-500 000 people die from hepatitis C and there is no curative medication for the chikungunya. Purpurealidin I is synthesized from tyrosine and tyramine parts, which will be put together to form an amide bond in the final step of the synthesis. The synthesis of purpurealidin I was not completed during the Master's thesis. However there were two purpurealidin I derivatives and four purpurealidin I tyramine part derivatives that were successfully synthesized. One of the compounds is purpurealidin E, which can be extracted from the sponge Pseudoceratina purpurea. The t-Boc derivative of purpurealidin E was examined against hepatitis C and chikungunya and the compound showed moderate activity against hepatitis C virus, but it wasn't active against chikungunya virus. The original plan to synthesize purpurealidin I is possible, although some reactions and purification of crude products need to be optimized in order to get better yields. For the future research derivatives of the t-Boc derivative of purpurealidin E should be synthesized and studied against hepatitis C virus.
  • Tilli, Irene (2017)
    Melanoma is the most severe case of skin cancer and there is no curative treatment if it has progressed. Despite the recent advances in drug therapy tens of thousands of patients die of melanoma annually. There is still need for new antimelanoma drugs for which marine compounds are a potential source. Halogens are common elements in drug molecules as they enhance their molecular properties. So far most of the halogenated drugs contain fluorine and/or chlorine but the role of bromine and iodine is probably growing in the future due to halogen bonding. Bromotyrosines are originally isolated from Verongiida-order sponges but whether they are truly of bacterial origin is under controversy. All bromotyrosine compounds consist of brominated tyrosine and/or tyramine residues or their derivatives. Purpurealidin I is one of the newest bromotyrosine derivatives extracted from Pseudoceratina purpurea and it has shown activity against melanoma. In this study eight new purpurealidin I derivatives were synthesized following a successful route previously designed. All synthesized derivatives contained the original N-oxime structure which's stereochemistry was determined to be E by X-ray crystallography. Cytotoxicity against A375 melanoma cells was determined for seven compounds synthesized here and for 15 compounds synthesized previously. All seven compounds and one previously synthesized purpurealidin I analog were active with CC50 values between 4,7 and 22,1 µM. The previously synthesized bromotyrosine derivative intermediates and aerophobin-1 analogs were not active. The selectivity of the active compounds was calculated by determining their CC50 value against Hs27 fibroblast cells. None of the compounds showed remarkable selectivity the most selective 2-pyridin containing derivative having four times better selectivity against melanoma. The tyrosine part and N-oxime seem to be important parts to preserve while the tyramine part can be modified more freely and maintain the activity. Still more derivatives need to be synthesized and tested to confirm these observations. More data is also needed considering the selectivity of the compounds.