Working Towards a Cancer Cell Selective and Brain Penetrating Anti Glioma Drug
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Glioblastoma multiforme is one of the most fatal and hardest to treat cancers. The main reasons for our failure to treat this type of cancer are the resistance to glioblastoma cells, to their high metastatic potential and poor drug penetration across the blood brain barrier. In previous research we have found that two alkaloids, lycorine and narciclasine, are effective in overcoming cancer cell resistance to apoptosis and potently inhibit glioblastoma cell growth and migration. In current research, described in this thesis, we attempted to take advantage of substrate active transport of lycorine and narciclasine into cancer cells as well as across the blood brain barrier using the GLUT1 transporter. To this end, we attempted to make various conjugates, of lycorine and narciclasine to glucose with the hypothesis that the glucose moiety would be recognized by GLUT1 and facilitate uptake of these molecules into brain cancer cells. Two such conjugates were successfully prepared and tested in cancer cells; however, it was found that these compounds were less potent than their parent alkaloids, suggesting that they were not good GLUT1 substrates.