College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, People's Republic of China.
J Chem Inf Model. 2011 Aug 22;51(8):1999-2006. doi: 10.1021/ci2002236. Epub 2011 Jul 26.
Heat shock protein 90 (Hsp90) takes part in the developments of several cancers. Novobiocin, a typically C-terminal inhibitor for Hsp90, will probably used as an important anticancer drug in the future. In this work, we explored the valuable information and designed new novobiocin derivatives based on a three-dimensional quantitative structure-activity relationship (3D QSAR). The comparative molecular field analysis and comparative molecular similarity indices analysis models with high predictive capability were established, and their reliabilities are supported by the statistical parameters. Based on the several important influence factors obtained from these models, six new novobiocin derivatives with higher inhibitory activities were designed and confirmed by the molecular simulation with our models, which provide the potential anticancer drug leads for further research.
热休克蛋白 90（Hsp90）参与了多种癌症的发展。新生霉素是 Hsp90 的一种典型的 C 端抑制剂，可能在未来被用作一种重要的抗癌药物。在这项工作中，我们基于三维定量构效关系（3D QSAR）探索了有价值的信息，并设计了新的新生霉素衍生物。建立了具有高预测能力的比较分子场分析和比较分子相似性指数分析模型，其可靠性得到了统计参数的支持。基于这些模型中获得的几个重要影响因素，设计了六个新的具有更高抑制活性的新生霉素衍生物，并通过分子模拟得到了验证，为进一步的研究提供了潜在的抗癌药物先导化合物。
