金属配合物药物（顺铂及其类似物）在临床上是一类非常重要且不可替代的抗癌药物，但该类药物靶向性有限、毒副作用严重等问题已经成为一个全球性课题。一种有效的解决策略是将具有靶向性的小分子配体与铂类药物进行结合形成靶向性抗肿瘤配合物，其药理性质显著优于单纯的小分子化合物或铂类药物。本项目以靶向性抗肿瘤金属配合物为研究对象，结合有机化学、药物化学及计算机辅助药物设计等前沿学科，基于单磷酸腺苷活化蛋白激酶（AMPK）抑制剂与金属配合物的研究现状，系统研究高特异性、低毒性的AMPK小分子抑制剂及其金属配合物的合理设计及合成、抗肿瘤活性、构效关系及结构优化等关键科学问题。项目预期获得一系列兼具小分子靶向性和金属配合物药物独特性质的抗肿瘤化合物并建立构效关系，为揭示AMPK在肿瘤发生及发展过程中的作用机制提供理论和技术支持，为开发新的靶向型抗肿瘤金属药物奠定基础。

Metal complexes drugs (cisplatin and its analogues) are vitally important and irreplaceable antcancer drugs in clinic, however, a growing global issue is that these drugs have some serious problems, such as limited target specific selectivity, serious toxic and side effects. An effective solving strategy is to integrate targeted small molecules as ligand with platinum drugs to form targeted antitumor complexes, which exhibit significantly better pharmacological properties than corresponding small molecules or platinum drugs. Therefore, this project will focus on the research of targeted antitumor metal complexes which is not only based on the current research status of adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitors and metal complex drugs, but also combined the academic frontiers of organic chemistry, medicinal chemistry and computer aided drug design. In addition, the key scientific issues including the rational drug design, antitumor activity, structure-activity relationship, structure optimization of AMPK small molecule inhibitors and their metal complexes with high specificity and activity will be systematically studied. This project is expected to obtain a series of AMPK inhibitors which exhibit both target ability of small molecule AMPK inhibitor and unique property of metal complexes, and establish structure-activity relationship. The results of this project are also hoped to provide theoretical and technological support for revealing the mechanism of AMPK in the process of tumor occurrence and development, and lay the foundation for developing targeted new antitumor metallic drugs.