具有抑制肥胖基因FTO生物功能的芳基金属抗癌配合物

肥胖基因(FTO)是近十年来的研究热点。FTO与肥胖及癌症密切相关，已发现可通过抑制FTO活性来阻止癌细胞增殖。研发FTO抑制剂有助于发现抗癌新药及发展抗癌新方法。目前仅发现有机小分子FTO抑制剂，配合物FTO抑制剂尚属空白。申请人发现芳基金属配合物可高效抑制FTO活性并具有优异抗癌活性，本项目将在此基础上，结合配合物在抗癌方面的独特优势，合成系列配合物FTO抑制剂，研究其与FTO的相互作用及机理，总结影响配合物抑制FTO活性、选择性的主要因素及其规律性，获得高选择性、高活性的配合物FTO抑制剂；研究配合物抑制FTO活性、选择性与其抗癌活性之间的关系及规律，确证FTO作为配合物抗癌新靶标，筛选同时具有高选择性抑制FTO活性、特异性抗癌功能的先导配合物。本项目的实施将为探索抗癌新靶点、新机理，及获得高抗癌活性配合物，高选择性、高活性配合物FTO抑制剂提供理论指导和物质基础。

The fat mass and obesity associated gene (FTO) has been a research hotspot in the past decade and achieved important breakthroughs. FTO is closely related to obesity and cancer, FTO-mediated m6A demethylation modification promotes tumorigenesis, and inhibition of FTO activity can inhibit cancer cell proliferation. Research and development of FTO inhibitors can help to suppress obesity, develop new anti-cancer drugs and develop new anti-cancer methods. At present, only small organic FTO inhibitors have been reported and the mechanism of their inhibition is unclear. The coordinative complex FTO inhibitors are still unexplored. The applicant has found that the coordinative complexes can inhibit FTO activity and has excellent anticancer activity. Based on this project, the interaction and mechanism of the coordinative complex FTO inhibitors upon FTO are studied, and the main factors affecting the activity and selectivity of the coordinative complexes to inhibit FTO and its regularity are summarized to obtain a highly selective and highly active coordinative complex FTO Inhibitors. The relationships and rules between the inhibition of FTO activity and selectivity and its anticancer activity were studied, and FTO was verified as a new anticancer target for the coordinative complex, and lead complexes with high selective and active inhibition of FTO and specific antitumor function was achieved. This project will provide theoretical guidance and material basis for exploring new anti-cancer targets, new mechanisms, and obtaining coordinative complexes with high anticancer activity, coordinative complex FTO inhibitors with high selectivity and high activity.