Synthesis and Characterization of Novel Colchicinoids as Potential Antitumoral Agents

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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.