糖尿病是极度影响人类健康及生活质量的常见病与多发病，而现有的降血糖药物疗效并不尽人意，糖尿病治疗仍然是困扰医学界的难题。本课题组在研究黄连碱衍生物的实验中，意外发现一类新型的9-羟基小檗碱类似物，具有较好的降血糖作用，通过分子对接发现该类化合物可能是通过激活磷酸化腺苷酸活化蛋白激酶AMPK，促使周围组织对葡萄糖吸收的增强从而达到降血糖目的，而AMPK磷酸化水平活性测定也进一步说明该类化合物是通过与AMPK的作用。在此基础上进一步利用分子对接的方法研究了该类化合物和AMPK靶点的结合模式，基于我们构效关系的初步研究成果，设计并拟合成能与AMPK特异性结合的四大类小分子，测定其体内外降血糖活性及毒性，并研究其作用机理，以期寻找到降血糖活性好、毒副作用低的治疗糖尿病的候选药物2~3个，有望解决困扰医药界治疗糖尿病的难题，并将为糖尿病的治疗创立新思路和新方法，具有极高的学术价值和应用价值。

Diabetes is extremely common and frequently encountered disease affecting human health and the quality of life. However, unsatisfactory efficacy of hypoglycemic drug blocks the progress of diabetes treatment. The research of coptisine derivatives in our group accidentally discovered a new class of 9-hydroxy berberine analogues with good hypoglycemic effect. The molecular docking found that these compounds can activate phosphorylated adenosine monophosphate activated protein kinase (AMPK), and then prompte glucose absorption by the surrounding tissue so as to achieve the purpose of lowering blood sugar. And levels of AMPK phosphorylation activity assay further illustrates this kind of compounds acts on AMPK. Based on the binding mode of compounds and AMPK targets by use of molecular docking methods, and the structure-activity relationship of preliminary research, we design four categories of small molecules with AMPK-specific binding property. After synthesizing these compounds, we will determine their lowering blood glucose activity and toxicity in vivo and in vitro, and study its mechanism, in order to find drug candidates with good lowering blood glucose activity, low toxicity and side effects in the treatment of diabetes. It is expected to solve the problem distressing medical profession, and will create new ideas and methods for the treatment of diabetes, which has high academic and application value.