Synthesis and Characterization of Novel Colchicinoids as Potential Antitumoral Agents

该项目旨在开发与天然产物秋水仙碱有关的新型微管蛋白结合抗肿瘤化合物（微管靶向剂）。 虽然秋水仙碱被用作治疗痛风和家族性地中海炎的药物，但由于其高全身毒性，秋水仙碱本身不能用于癌症治疗。 基于广泛且非常有前途的初步研究，将合成一系列具有改变的支架结构（和可变C-7侧链）的新型秋水仙碱类似物。此外，将制备“反应性”秋水仙素，其能够共价连接到蛋白质靶标。除了开发强大的合成（基于广泛的现代，通常是金属催化方法），以实现设想的结构，化合物的生物学和药理学潜力将被研究-与医学合作伙伴密切合作。通过这种方式，将推导出结构-活性关系，并将鉴定出特别有效的（活性和选择性）化合物用于进一步的生物学研究。

The project aims at the development of novel tubulin-binding antitumoral compounds (microtubule-targeting agents), which are related to the natural product colchicine. While used as a drug against gout and famiial mediterranian feaver, colchicine itself cannot be used in cancer therapy because of its high general toxicity. Based on extensive and highly promising preliminary studies, a series of novel colchicine analogs with altered scaffold structures (and variable C-7 side chains) will be synthesized. Furthermore, "reactive" colchicinoids will be prepared, which are able to covalently attach to the protein target. Besides the development of powerful syntheses (based on a broad spectrum of modern, often metal-catalytic methods) towards the envisioned structures, the biological and pharmacological potential of the compounds shall be investigated - in close cooperation with partners from medicine. This way, structure-activity relationships will be derived, and particularly effective (active and selective) compounds will be identified for further biological studies.