基于预测配体的药物设计方法对苯并噻嗪类HDAC8抑制剂的比较定量结构评估。

IF 2.3 3区 环境科学与生态学 Q3 CHEMISTRY, MULTIDISCIPLINARY
S Banerjee, S K Baidya, N Adhikari, T Jha
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引用次数: 0

摘要

组蛋白去乙酰化酶8 (HDAC8)是一个被证实与包括癌症在内的多种疾病相关的生物分子靶点。虽然几种HDAC抑制剂对这些疾病有效,但迄今为止没有选择性HDAC8抑制剂被批准。因此,开发有效的hdac8选择性抑制剂是对抗此类疾病的必然选择。在这里,一些苯并噻嗪衍生的HDAC8抑制剂被考虑用于比较QSAR分析,这可能阐明负责调节其功效的主要结构成分。这些不同建模技术的几个结果相互证明,从而相互验证。基于配体的药效团模型研究确定了环芳香族、正离子化和疏水性特征是抑制HDAC8的基本结构属性。此外,MLR、HQSAR和基于现场的3D-QSAR研究表明,正离子化和疏水特性对hdac - 8的有效抑制具有实用价值。同样,基于现场的3D-QSAR研究为融合苯基环的取代提供了有用的见解。此外,本次观测也验证了之前报道的分子对接观测结果。在此基础上,设计并预测了一些新分子。因此,对这些HDAC8抑制剂的比较结构分析,必将有助于未来开发有效的HDAC8抑制剂作为有前景的抗癌治疗药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A comparative quantitative structural assessment of benzothiazine-derived HDAC8 inhibitors by predictive ligand-based drug designing approaches.

Histone deacetylase 8 (HDAC8) is a verified biomolecular target associated with diverse diseases including cancer. Though several HDAC inhibitors emerged effective against such diseases, no selective HDAC8 inhibitor is approved to date. Therefore, the development of potent HDAC8-selective inhibitors is inevitable to combat such diseases. Here, some benzothiazine-derived HDAC8 inhibitors were considered for a comparative QSAR analysis which may elucidate the prime structural components responsible for modulating their efficacy. Several outcomes from these diverse modelling techniques justified one another and thus validated each other. The ligand-based pharmacophore modelling study identified ring aromatic, positive ionizable, and hydrophobic features as essential structural attributes for HDAC8 inhibition. Besides, MLR, HQSAR and field-based 3D-QSAR studies signified the utility of the positive ionizable and hydrophobic features for potent HDAC8 inhibition. Again, the field-based 3D-QSAR study provided useful insight regarding the substitution in the fused phenyl ring. Moreover, the current observations also validated the previously reported molecular docking observations. Based on the outcomes, some new molecules were designed and predicted. Therefore, this comparative structural analysis of these HDAC8 inhibitors will surely assist in the development of potent HDAC8 inhibitors as promising anticancer therapeutics in the future.

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来源期刊
CiteScore
5.20
自引率
20.00%
发文量
78
审稿时长
>24 weeks
期刊介绍: SAR and QSAR in Environmental Research is an international journal welcoming papers on the fundamental and practical aspects of the structure-activity and structure-property relationships in the fields of environmental science, agrochemistry, toxicology, pharmacology and applied chemistry. A unique aspect of the journal is the focus on emerging techniques for the building of SAR and QSAR models in these widely varying fields. The scope of the journal includes, but is not limited to, the topics of topological and physicochemical descriptors, mathematical, statistical and graphical methods for data analysis, computer methods and programs, original applications and comparative studies. In addition to primary scientific papers, the journal contains reviews of books and software and news of conferences. Special issues on topics of current and widespread interest to the SAR and QSAR community will be published from time to time.
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