Synthesis and Characterization of Novel Colchicinoids as Potential Antitumoral Agents

作为潜在抗肿瘤药物的新型秋水仙碱类化合物的合成和表征

• 批准号: 259604358
• 负责人: Professor Dr. Hans-Günther Schmalz
• 金额: --
• 依托单位: Kinder- und Jugendmedizin - Onkologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/259604358?language=en
• 关键词: Synthesis; Characterization; Novel; Colchicinoids; Potential

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.

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。 基于广泛的和非常有前途的初步研究，一系列新的秋水仙碱类似物与改变支架结构（和可变的C-7侧链）将被合成。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。

项目成果

Synthesis of Nonracemic Pyrrolo‐allocolchicinoids Exhibiting Potent Cytotoxic Activity

具有有效细胞毒活性的非外消旋吡咯并别秋水仙碱类化合物的合成

• DOI: 10.1002/ejoc.201601069
• 发表时间: 2016
• 期刊: European Journal of Organic Chemistry
• 影响因子: 2.8
• 作者: Shchegravina;Knyazev;Beletskaya;Svirshchevskaya;Schmalz;Fedorov
• 通讯作者: Fedorov

A Facile Synthetic Approach to Nonracemic Substituted Pyrrolo-allocolchicinoids Starting from Natural Colchicine

以天然秋水仙碱为原料制备非外消旋取代的吡咯别别秋水仙素的简便合成方法

• DOI: 10.1055/s-0037-1610673
• 发表时间: 2019
• 期刊: Synthesis
• 作者: Shchegravina;Svirshchevskaya;Schmalz;Fedorov
• 通讯作者: Fedorov

Synthesis and antitumor activity of 7-(triazol-1-yl)pyrroloallocolchicine derivatives

7-(三唑-1-基)吡咯并别秋水仙碱衍生物的合成及其抗肿瘤活性

• DOI: 10.1007/s11172-015-1018-z
• 发表时间: 2015
• 期刊: Russian Chemical Bulletin
• 影响因子: 1.7
• 作者: Sitnikov;Sintsov;Shchegravina;Prokop;Schmalz;Fedorov;A. Yu.
• 通讯作者: A. Yu.

Synthesis of indole-derived allocolchicine congeners exhibiting pronounced anti-proliferative and apoptosis-inducing properties

吲哚衍生的同系物秋水仙碱同系物的合成，具有显着的抗增殖和细胞凋亡诱导特性

• DOI: 10.1039/c5md00320b
• 发表时间: 2015
• 期刊: MedChemComm
• 作者: Sitnikov;Sinzov;Allegro;Barbier;Combes;Onambele;Prokop;Schmalz;Fedorov
• 通讯作者: Fedorov

Synthesis of New Sulfur-Containing Derivatives of Furanoallocolchicinoids

• DOI: 10.1134/s1070428016080078
• 发表时间: 2016-08-01
• 期刊: RUSSIAN JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 0.8
• 作者: Gracheva, Yu. A.;Schmalz, H. -G.;Fedorov, A. Yu.
• 通讯作者: Fedorov, A. Yu.