Target Based Designing of Anthracenone Derivatives as Tubulin Polymerization Inhibiting Agents: 3D QSAR and Docking Approach.

International Journal of Medicinal Chemistry Pub Date : 2014-01-01 Epub Date: 2014-04-17 DOI:10.1155/2014/658016
Abdul Samad, Moawiah M Naffaa, Mohammed Afroz Bakht, Manav Malhotra, Majid A Ganaie
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引用次数: 7

Abstract

Novel anthracenone derivatives were designed through in silico studies including 3D QSAR, pharmacophore mapping, and molecular docking approaches. Tubulin protein was explored for the residues imperative for activity by analyzing the binding pattern of colchicine and selected compounds of anthracenone derivatives in the active domain. The docking methodology applied in the study was first validated by comparative evaluation of the predicted and experimental inhibitory activity. Furthermore, the essential features responsible for the activity were established by carrying out pharmacophore mapping studies. 3D QSAR studies were carried out for a series of 1,5- and 1,8-disubstituted10-benzylidene-10H-anthracen-9-ones and 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-one derivatives for their antiproliferation activity. Based on the pattern recognition studies obtained from QSAR results, ten novel compounds were designed and docked in the active domain of tubulin protein. One of the novel designed compounds "N1" exhibited binding energy -9.69 kcal/mol and predicted Ki 78.32 nM which was found to be better than colchicine.

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基于靶标设计蒽酮类微管蛋白聚合抑制剂:三维QSAR与对接方法。
新的蒽酮衍生物通过计算机研究设计,包括3D QSAR,药效团定位和分子对接方法。通过分析秋水仙碱和蒽酮衍生物在活性区域的结合模式,探索微管蛋白活性所需的残基。首先通过对预测抑制活性和实验抑制活性的比较评价验证了研究中采用的对接方法。此外,通过开展药效团作图研究,确定了负责活性的基本特征。对一系列1,5-和1,8-二取代10-苄基- 10h -蒽-9- 1和10-(2-氧-2-苯乙基)- 10h -蒽-9- 1衍生物进行了三维QSAR研究,以确定其抗增殖活性。基于从QSAR结果中获得的模式识别研究,设计了10个新的化合物并停靠在微管蛋白的活性区域。新设计的化合物N1的结合能为-9.69 kcal/mol,预测Ki值为78.32 nM,优于秋水仙碱。
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期刊介绍: International Journal of Medicinal Chemistry is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles in all areas of chemistry associated with drug discovery, design, and synthesis. International Journal of Medicinal Chemistry is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles in all areas of chemistry associated with drug discovery, design, and synthesis.
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