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Binding Mode Prediction and Identification of New Lead Compounds from Natural Products as 3-OST Enzyme Inhibitors
Letters in Drug Design & Discovery ( IF 1 ) Pub Date : 2020-08-31 , DOI: 10.2174/1570180817666200313105944
Rui Sousa 1 , Narayana Subbiah Hari Narayana Moorthy 1 , Pedro Alexandrino Fernandes 1 , Maria Joao Ramos 1 , Natércia Fernandes Brás 1
Affiliation  

Background and Introduction: The availability of antiviral medicines for the treatment of viral diseases is limited, hence the discovery of novel bioactive molecules is required. The present investigation has been carried out to develop novel 3-O-sulfotransferase enzyme inhibitors to treat viral diseases.

Methods: Virtual screening study (QSAR, docking and pharmacophore analysis) and binding mode analysis have been performed on a dataset collected from the literature (synthetic and natural compounds).

Results and Discussion: The docking studies showed that Glu184, His186, Lys215 and Lys368 residues established the most important hydrogen bonding with several hit compounds. The QSAR results explained that the presence of electronegative atoms/groups in the aromatic or heteroaromatic rings confer increased activity. Furthermore, the flexibility and the aromatic rings with less polar groups have better activity than the compounds connected to purine rings. Finally, the structurebased pharmacophore studies illustrated that the ligand has many polar interaction sites, and the projected acceptor and donor groups in the molecules make a significant contribution to the pharmacophore model building.

Conclusion: These studies identified two compounds, Phomoidride B and Barceloneic acid A, as potential 3-OST inhibitors.



中文翻译:

天然产物中新的先导化合物作为3-OST酶抑制剂的结合模式预测和鉴定

背景与简介:抗病毒药物在治疗病毒性疾病方面的可用性有限,因此需要发现新型的生物活性分子。已经进行了本研究以开发用于治疗病毒性疾病的新型3-O-磺基转移酶抑制剂。

方法:已对从文献(合成和天然化合物)收集的数据集进行了虚拟筛选研究(QSAR,对接和药效团分析)和结合模式分析。

结果与讨论:对接研究表明,Glu184,His186,Lys215和Lys368残基与几种命中化合物建立了最重要的氢键。QSAR结果解释了芳族或杂芳族环中带负电原子/基团的活性增加。此外,柔韧性和具有较少极性基团的芳环比与嘌呤环连接的化合物具有更好的活性。最后,基于结构的药效团研究表明,配体具有许多极性相互作用位点,并且分子中预计的受体和供体基团对药效团模型的建立起了重要作用。

结论:这些研究确定了潜在的3-OST抑制剂Phomoidride B和Barceloneic acid A这两种化合物。

更新日期:2020-08-31
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