Marzaro Giovanni, Chilin Adriana
Department of Pharmaceutical and Pharmacological Science, University of Padova, via Marzolo 5, I- 35131 Padova, Italy.
Curr Top Med Chem. 2014;14(20):2253-62. doi: 10.2174/1568026614666141130092853.
Microtubules are high dynamic protein filaments fundamental for cells growth and proliferation. Hence, tubulin inhibitors are useful anticancer compounds. Three major binding site have been identified in tubulin, on the basis of known ligands: the vinca domain, the colchicine domain and the taxane domain. Several compounds able to bind the colchicine and the taxane domains have been to date synthesized and evaluated. In this review we give a description of the developed QSAR and 3D-QSAR models, giving particular attention to those studies that give structural insight in the binding modes of compounds with the target.
微管是细胞生长和增殖所必需的高度动态的蛋白质细丝。因此,微管蛋白抑制剂是有用的抗癌化合物。根据已知配体,在微管蛋白中已鉴定出三个主要结合位点:长春花碱结构域、秋水仙碱结构域和紫杉烷结构域。迄今为止,已经合成并评估了几种能够结合秋水仙碱和紫杉烷结构域的化合物。在这篇综述中,我们描述了已开发的定量构效关系(QSAR)和三维定量构效关系(3D-QSAR)模型,特别关注那些能深入了解化合物与靶点结合模式的结构研究。