Hydropathic analysis and biological evaluation of stilbene derivatives as colchicine site microtubule inhibitors with anti-leukemic activity.
Hydropathic analysis and biological evaluation of stilbene derivatives as colchicine site microtubule inhibitors with anti-leukemic activity.
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DOI：
10.3109/14756360902787055
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发表时间：
2009-12
影响因子：
5.6
通讯作者：
Kellogg GE
中科院分区：
文献类型：
--
作者：
Tripathi A;Durrant D;Lee RM;Baruchello R;Romagnoli R;Simoni D;Kellogg GE
微管在细胞分裂中的关键作用已经将微管蛋白确定为开发癌症治疗剂的靶标;特别是微管蛋白是通过干扰微管的动态稳定性起作用的抗肿瘤剂的靶标。进行了分子模拟研究，以准确地表示在αβ-微管蛋白秋水仙碱位点结合的一类新的基于二苯乙烯的微管蛋白抑制剂的复合物结构和结合模式。计算对接沿着HINT得分分析将这些抑制剂拟合到秋水仙碱位点，并揭示了对抑制剂设计有用的详细结构活性信息。结果的定量分析与这些衍生物的体外抗增殖活性（范围为3 nM至100 μM）非常一致，因此计算和测量的结合自由能与0.89（标准误差± 0.85 kcal mol−1）的r2相关。这种相关性表明，未知化合物的活性可以预测。
The crucial role of the microtubule in the cell division has identified tubulin as a target for the development of therapeutics for cancer; in particular tubulin is a target for antineoplastic agents that act by interfering with the dynamic stability of microtubules. A molecular modeling study was carried out to accurately represent the complex structure and the binding mode of a new class of stilbene-based tubulin inhibitors that bind at the αβ-tubulin colchicine site. Computational docking along with HINT score analysis fitted these inhibitors into the colchicine site and revealed detailed structure-activity information useful for inhibitor design. Quantitative analysis of the results was in good agreement with the in vitro antiproliferative activity of these derivatives (ranging from 3 nM to 100 μM) such that calculated and measured free energies of binding correlate with an r2 of 0.89 (standard error ± 0.85 kcal mol−1). This correlation suggests that the activity of unknown compounds may be predicted.
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影响因子：
7.3
作者：
Cozzini, P;Fornabaio, M;Mozzarelli, A
通讯作者：
Mozzarelli, A
影响因子：
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作者：
Tripathi, Ashutosh;Fornabaio, Micaela;Mooberry, Susan L.
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作者：
Jones, G;Willett, P;Taylor, R
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Taylor, R