蒽环类抗生素和核苷类药物是作用于DNA但作用机制不同的抗肿瘤和抗病毒药物，在癌症及病毒感染的治疗中均占有极为重要的地位,但一些伴随的毒副作用和越来越严重的耐药性，大大影响了它们临床使用效果。本项目拟以Top-DNA-drug三重复合物和耐药性蛋白p-gp的结构为模型的计算机分子模拟及分子对接虚拟筛选技术设计、合成系列蒽醌并三（咪）唑核苷类似物。它们既是蒽环类药物的类似物又是多环三（咪）唑核苷类似物，兼具蒽环及核苷的独特结构，期望通过不同的作用机制共同发挥作用和相互协作，达到提高活性、降低毒副作用和耐药性的目的。通过对这些杂化体的抗肿瘤及抗病毒活性以及荧光活性研究，以期发现具有更好药物特性的新型先导化合物，以及可用于核酸和蛋白质检测的高灵敏的荧光探针。

The anthracyclines and nucleoside drugs are among the most potent and clinically used in virus infection and cancer therapy. The primary cellular targets for anthracyclines and nucleosides are DNA through different mechanisms of action. Although anthracyclines are widely used in cancer therapy, two major problems, drug resistance and cardiotoxicity,limit their effective clinical application. In this proposal, syntheses and bioactivities of a series of nucleoside analogues of anthra[2,3-d][1,2,3]tri-/imid-azole-5,10-dione will be investigated. The rational design of these new hybrids of anthracyclines and nucleosides is based on the molecular simulation and the docking of these molecules with Top-DNA-drug triple complexes and mammalian P-gp protein structural models.The target compounds possess novel structural properties: both anthracycline-like and nucleoside-like.We expect this research will provide us with precious structure-activity relationship information and new lead compounds or drug candidates, and highly sensitive fluoresence probes for detecting DNA and proteins.