Gupta Suvroma, Bhattacharyya Bhabatarak
Department of Biochemistry, Bose Institute, Centenary Campus, Calcutta, India.
Mol Cell Biochem. 2003 Nov;253(1-2):41-7. doi: 10.1023/a:1026045100219.
Studies on vinca domain binding drugs were done in great details by a number of workers as it is recognized as a potential target for anticancer drug development. Their structures, properties, mode of action, success and failures as potential anticancer drug have been discussed in short details in this review. Among these drugs rhizoxin and maytansine are competitive inhibitors, and bind at the vinblastine binding site of tubulin where as others are non-competitive inhibitors. Besides binding, these drugs also differ in the extent of GTP hydrolysis, GTP exchange and in the stabilization of colchicine binding site. The toxicity level of these drugs towards the host cells and the extent of efflux of drugs by the P-glycoprotein mediated pump are also discussed.
许多研究人员对长春花结构域结合药物进行了详细研究，因为它被认为是抗癌药物开发的一个潜在靶点。在这篇综述中，简要讨论了它们作为潜在抗癌药物的结构、性质、作用方式、成功与失败之处。在这些药物中，根霉素和美登素是竞争性抑制剂，它们结合在微管蛋白的长春碱结合位点，而其他药物是非竞争性抑制剂。除了结合之外，这些药物在GTP水解、GTP交换以及秋水仙碱结合位点的稳定性方面也存在差异。还讨论了这些药物对宿主细胞的毒性水平以及P-糖蛋白介导的泵对药物的外排程度。
