| Heparan sulfate (HS) is involved in many pathological processes of breast cancer. The component and distribution of sulfates in HS are of great importance to proliferation of breast cancer cells and angiogenesis. With the investigation of the mechanism of growth factors modulated by HS, the development and application of heparan sulfate polysaccharide analogs became the hotspot.Polysaccharides, from nature production and chemosynthesis, share the same structure features with HS and supply lots of chemical groups that can be modified. Polysaccharides derivatives, obtained via introduction of different kinds of functional groups into polysaccharides, make a large molecule library for anti-breast cancer development.Based on the structure-function relationship, we found that designing and preparing polysaccharides with specific arrangement of functional groups is an effective way to enhance the antitumour activity of these moleculars. Introduction of nonsulfate groups can avoid the side effects of these polysaccharids, for too many sulfates can influence the normal function of HS.We first prepared a dextran derivative, NDP-5-1, by adding hydroxyl and benzylmide groups to dextran chain. With MTT assay, we found NDP-5-1 significantly inhibited the growth of breast cancer cells. Then, on base the leading compound of NDP-5-1, we further redesigned the molecular by changing the length of side chains and introducing polar groups. Two more effective compounds, NDP-3-1,NDP-2-2, were obtained, with the IC50 of 0.1893μmol/L and 0.1860μmol/L respectively in 3H-thymidine incorporation assay.To improve the potential of drug development of functional polysaccharides, we designed some chitosan derivatives and studied their synthesis. By controlling the reaction conditions, we studied the chemical properties of these compounds. With ~3H-thymidine incorporation assay, we found that most of the chitosan derivatives could effectively inhibit the growth of breast cancer cells.
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