新疆胀果甘草黄酮类成分及合成衍生物的制备、对肿瘤干细胞标记物的影响、抗宫颈癌活性及作用机制研究

子宫颈癌是女性重大肿瘤，也是新疆地方性高发疑难症。从天然药物中寻找新型抗癌先导化合物在宫颈癌药物干预治疗及防治复发转移中具有重要意义。在前期研究中发现新疆胀果甘草黄酮类单体明显抑制宫颈癌细胞增殖，并显著影响宫颈癌干细胞标记物的表达，显示较强抗癌活性，而对正常细胞的毒性低。本课题：1.对新疆胀果甘草乙醇提取物进行制备，对甘草查尔酮类5个单体成分进行分离鉴定、体外抗癌活性及其机制研究；2.对结构独特的先导化合物进行筛选并做化学修饰，制备氟代、氨代和a-甲基化查尔酮衍生物（约15个）、做药理筛选和构效关系分析，对活性高的候选药物进行筛选；3.对选定化合物在宫颈癌细胞信号通路中的作用靶点进行研究，对作用机制进行阐明，尤其对癌基因调控机制及对宫颈癌干细胞的干预作用进行研究，从而筛选新型宫颈癌分子靶向治疗候选药物，为有效低毒的新型抗宫颈癌创新药物筛选及对地区性重大疾病宫颈癌的有效药物干预奠定基础。

Cervical cancer is an important disease in the word in women cancer, it is also the major difficult disease in Xinjiang local women. The search for new natural anti-cancer leading compound is important in new drug research for intervention treatment and prevention of recurrence and metastasis of cervical cancer. In the previous study, we found that, the flavonoid monomer from Xinjiang Glycyrrhiza inflata (XGI) can significantly inhibit the proliferation of human cervical cancer cells, induce cancer cell apoptosis, and inhibit the expression of cancer steem cells markers, then showed an important therapeutic study interest. In this research project, we perform, in the basis of preliminary study: 1.To screen the anti-cervical cancer active part of flavonoid extracts; to analysis anticancer effective components and active monomers; to prepare XGI standardized extract containing higher effective component; 2. To search active lead compound for chemical structure modification for synthesizing fluorized, aminized and a-methylized chalcone derivatives for structure-activity relationship studies and for screening new active drugs with improved anticancer activity; 3. To study the potential intervention feature of the XGI specie specific monomer licochalcone A and related derivatives to the cervical cancer steam cells markers, and the toxicological characteristics, as well as the potential drug targets, molecular mechanisms in tumor cell signaling pathways to promote apoptosis. This study has important value in the progressive study on the anticancer activity of flavonoid components form Xinjiang medicinale plant XGI for screening the new anti-cancer candidate drug and performing the effective drug intervention treatment of cervical cancer disease with highly incidence.