3D-QSAR辅助的新生霉素类似物的设计、合成与评价
3D-QSAR Assisted Design, Synthesis and Evaluation of Novobiocin Analogues.
作者信息
Zhao Huiping, Moroni Elisabetta, Yan Bin, Colombo Giorgio, Blagg Brian S J
机构信息
Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, Kansas 66045-7563, USA.
出版信息
ACS Med Chem Lett. 2012 Jan 1;4(1):57-62. doi: 10.1021/ml300275g.
Abstract
Hsp90 is an attractive therapeutic target for the treatment of cancer. Extensive structural modifications to novobiocin, the first Hsp90 C-terminal inhibitor discovered, have produced a library of novobiocin analogues and revealed some structure-activity relationships. Based upon the most potent novobiocin analogues generated from prior studies, a three-dimensional quantitative structure-activity (3D-QSAR) model was built. In addition, a new set of novobiocin analogues containing various structural features supported by the 3D-QSAR model were synthesized and evaluated against two breast cancer cell lines. Several new inhibitors produced anti-proliferative activity at mid nano-molar concentrations, which results through Hsp90 inhibition.
摘要
热休克蛋白90（Hsp90）是癌症治疗中一个具有吸引力的治疗靶点。对新霉素（首个被发现的Hsp90 C端抑制剂）进行了广泛的结构修饰，生成了一个新霉素类似物文库，并揭示了一些构效关系。基于先前研究中产生的最有效的新霉素类似物，构建了一个三维定量构效（3D-QSAR）模型。此外，合成了一组新的含有3D-QSAR模型支持的各种结构特征的新霉素类似物，并针对两种乳腺癌细胞系进行了评估。几种新的抑制剂在中纳摩尔浓度下产生了抗增殖活性，这是通过抑制Hsp90实现的。
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本文引用的文献
1
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ACS Med Chem Lett. 2012 Apr 12;3(4):327-331. doi: 10.1021/ml300018e. Epub 2012 Feb 26.
2
Hsp90 modulation for the treatment of Alzheimer's disease.
Adv Pharmacol. 2012;64:1-25. doi: 10.1016/B978-0-12-394816-8.00001-5.
3
Synthesis and Evaluation of Noviose Replacements on Novobiocin that Manifest Anti-proliferative Activity.
ACS Med Chem Lett. 2010 Jul 13;1(7):311-315. doi: 10.1021/ml100070r.
4
Engineering an antibiotic to fight cancer: optimization of the novobiocin scaffold to produce anti-proliferative agents.
J Med Chem. 2011 Jun 9;54(11):3839-53. doi: 10.1021/jm200148p. Epub 2011 May 9.
5
Hallmarks of cancer: the next generation.
Cell. 2011 Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013.
6
Identification and initial SAR of silybin: an Hsp90 inhibitor.
Bioorg Med Chem Lett. 2011 May 1;21(9):2659-64. doi: 10.1016/j.bmcl.2010.12.088. Epub 2010 Dec 28.
7
Heat shock protein 90: inhibitors in clinical trials.
J Med Chem. 2010 Jan 14;53(1):3-17. doi: 10.1021/jm9004708.
8
Suitability of GRIND-based principal properties for the description of molecular similarity and ligand-based virtual screening.
J Chem Inf Model. 2009 Sep;49(9):2129-38. doi: 10.1021/ci900228x.
9
The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity.
J Org Chem. 2008 Nov 21;73(22):8901-20. doi: 10.1021/jo801312r. Epub 2008 Oct 22.
10
Development and validation of AMANDA, a new algorithm for selecting highly relevant regions in Molecular Interaction Fields.
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