白藜芦醇新型衍生物预防大肠癌的体内外作用及机制

The morbility and mortality of colorectal cancer are ranked the top three malignancies. Compared with 1975, in 2000 the colorectal cancer mortality of America decreased by 26%. It is worth noting that only 3% decline in mortality due to treatment or tertiary prevention, the remaining 23% due to decrease the degree of exposure in colorectal cancer risk factors or primary prevention and to carry out the screening work or secondary prevention. Chemopreventive agent is currently one of the hot areas of colorectal cancer, inflammation is an important factor in the development of mediated tumorigenesis. Pharmacological effects of resveratrol has anti-inflammatory, antioxidant and anti-free radicals. Resveratrol inhibits tumor in the initiation, promotion and development stages, it is a potential cancer chemopreventive. However, resveratrol is not from the laboratory to clinical practice. Because oral resveratrol is difficult to achieve the effect concentration of anti-cancer or cancer preventive in vivo. Further improve the efficacy of resveratrol is the forefront of current research. In this study, designed and synthesized 29 kinds of new resveratrol derivatives, in order to filter out the low toxicity of the drug, which can prevent colorectal cancer, so as to achieve an objective of primary prevention.

结直肠癌的发病率及死亡率均排恶性肿瘤前三位。与1975年相比，2000年美国大肠癌的死亡率下降了26%。值得注意的是，死亡率的下降仅有3%是因为治疗手段（三级预防）的进步，剩余的23%归功于大肠癌危险因子暴露度的减少（一级预防）和筛查工作的开展（二级预防）。化学预防剂是目前大肠癌领域的研究热点之一，炎症是介导肿瘤发生发展的重要因素。白藜芦醇具有抗炎、抗氧化和抗自由基的药理作用，在肿瘤的起始、促进和发展阶段均具有抑制作用，是一种潜在的恶性肿瘤化学预防剂。但白藜芦醇并未从实验室走向实际临床应用，因为口服白藜芦醇体内难以达到抗癌或预防癌作用的浓度。进一步提高白藜芦醇的疗效是目前研究的前沿。本研究运用结构拼合方法，设计合成了29种全新的白藜芦醇衍生物，以期筛选出高效低毒的能预防大肠癌的药物，从而达到一级预防的目的。