ColBioS-FlavRC: A Collection of Bioselective Flavonoids and Related Compounds Filtered from High-Throughput Screening Outcomes
ColBioS-FlavRC: A Collection of Bioselective Flavonoids and Related Compounds Filtered from High-Throughput Screening Outcomes
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DOI：
10.1021/ci5002668
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发表时间：
2014-08-01
影响因子：
5.6
通讯作者：
Kurunczi, Ludovic
中科院分区：
文献类型：
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作者：
Avram, Sorin I.;Pacureanu, Liliana M.;Kurunczi, Ludovic
黄酮类化合物是天然多酚类化合物中最广泛的一类，因其对人体健康的多种益处而受到广泛研究。由于它们的物理化学或生物学特性，许多代表被认为在各种蛋白质靶点之间表现出低选择性或困扰高通量筛选（HTS）结果。本研究的目的是突出可靠的，生物选择性的化合物，共享黄烷醇类化合物在HTS实验中的支架。应用过滤方案从确证性Pub Chem生物测定中去除不需要的类黄酮（和相关化合物）。433种针对各种蛋白质靶点的化合物构成了生物选择性类黄酮和相关化合物（ColBioS-FlavRC）集合的核心。ColBioS-FlavRC还额外添加了2908种非活性相关化合物，为方法优化和验证提供了依据。我们通过药效团建模举例说明了ColBioS-FlavRC的使用，随后（外部）验证用于虚拟筛选目的。药效团假设的早期富集能力通过中位指数检索操作曲线富集（MeROCE）进行测量，这是虚拟筛选方法比较评价中的一个合适指标。ColBioS-FlavRC可在支持信息中获得，并可免费获得以进行进一步研究。
Flavonoids, the vastest class of natural polyphenols, are extensively investigated for their multiple benefits on human health. Due to their physicochemical or biological properties, many representatives are considered to exhibit low selectivity among various protein targets or to plague high-throughput screening (HTS) outcomes. The aim of this study is to highlight reliable, bioselective compounds sharing flavonoidic scaffolds in HTS experiments. A filtering scheme was applied to remove undesired flavonoids (and related compounds) from confirmatory Pub Chem bioassays. A number of 433 compounds addressing various protein targets form the core of the collection of bioselective flavonoids and related compounds (ColBioS-FlavRC). With an additional set of 2908 inactive related compounds, ColBioS-FlavRC offers the grounds for method optimization and validation. We exemplified the use of ColBioS-FlavRC by pharmacophore modeling, subsequently (externally) validated for virtual screening purposes. The early enrichment capabilities of the pharmacophore hypotheses were measured by means of the median exponential retriever operating curve enrichment (MeROCE), a suited metric in comparative evaluations of virtual screening methods. ColBioS-FlavRC is available in the Supporting Information and is freely accessible for further studies.