| Summary: | 碩士 === 國立中正大學 === 化學暨生物化學研究所 === 107 === According to cause of death statistics in ministry of health and welfare, cancer is the most lethal disease. Cancer metastasis is the major cause of death in cancer patients. In previous study, overexpression of sialic acids on the tumor cell surface is a hallmark of cancer, and the upregulation of sialyltransferase activity is associated with cancer metastasis. Sialic acids are monosaccharides, found as terminal unit on the cell surface and should be recognized by siglecs on the immune cells. Sialyltransferases are one of glycosyltransferases, and can transfer sialic acids to glycoproteins or glycolipids. Building on these the results, we want to develop the sialyltransferase inhibitor to retard sialic acid transferring to the cell surface leading to. Reduction of cancer cell growth and suppression of cancer metastasis.
Here, we synthesized a new and novel skeleton based on homolithocholic acid, lithocholic acid-analogue, where the structure possessed NBD group and different linkers of N3. The IC50 values of homolithocholic acid analogues are around the range of 6-14 μM against N-glycan ST6GAL1. Furthermore, they did not block the sialylation of O-glycan ST3GAL1, suggesting that this series of sialyltransferase inhibitors demonstrate their specific selectivity toward N-Glycan sialylation versus O-Glycan sialylation. In addition, homolithocholic acid analogues had cytotoxicity, when MTT assays tested under the culture condition without serum. The results of anti-migration effects derived from homolithocholic acid analogues indicated that cytotoxicity is the main reason for the action of mechanism.
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