两步法合成康普瑞汀 A-4 及其衍生物作为有效的微管组装抑制剂。
A 2-step synthesis of Combretastatin A-4 and derivatives as potent tubulin assembly inhibitors.
机构信息
Biomedical Research Centre, Kidscan Laboratories, School of Science, Engineering and Environment, University of Salford, Salford, UK.
Central Laser Facility, Research Complex at Harwell, Rutherford Appleton Laboratory, STFC, Chilton, Oxfordshire OX11 0QX, UK.
出版信息
Bioorg Med Chem. 2020 Oct 1;28(19):115684. doi: 10.1016/j.bmc.2020.115684. Epub 2020 Aug 5.
A series of combretastatin derivatives were designed and synthesised by a two-step stereoselective synthesis by use of Wittig olefination followed by Suzuki cross-coupling. Interestingly, all new compounds (2a-2i) showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, 2a, 2b and 2e were the most active across three cancer cell lines. In addition, these compounds inhibited the polymerisation of tubulin in vitro more efficiently than CA-4. They caused cell cycle arrest in G/M phase further confirming their ability to inhibit tubulin polymerisation.
设计并合成了一系列的 combretastatin 衍生物，采用两步立体选择性合成法，通过Wittig 烯丙基化反应和Suzuki 交叉偶联反应。有趣的是，所有新化合物（2a-2i）在纳摩尔浓度下均显示出很强的基于细胞的抗增殖活性。在这些化合物中，2a、2b 和 2e 在三种癌细胞系中最为活跃。此外，这些化合物在体外比 CA-4 更有效地抑制微管蛋白的聚合。它们导致细胞周期停滞在 G/M 期，进一步证实了它们抑制微管蛋白聚合的能力。
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