Curpăn Ramona, Avram Sorin, Vianello Robert, Bologa Cristian
Department of Computational Chemistry, Institute of Chemistry Timisoara of Romanian Academy, 24 Mihai Viteazul, Timisoara 300223, Romania.
Department of Computational Chemistry, Institute of Chemistry Timisoara of Romanian Academy, 24 Mihai Viteazul, Timisoara 300223, Romania.
Bioorg Med Chem. 2014 Apr 15;22(8):2461-8. doi: 10.1016/j.bmc.2014.02.055. Epub 2014 Mar 12.
The goal of this study is the understanding of biologically promiscuous compounds (frequent hitters) in HTS outcomes through their chemical behavior estimated via reactivity descriptors. Chemical reactivity is often an undesirable property due to the lack in biological selectivity of compounds comprised in HTS libraries. In this study the reactivity indexes have been computed within the DFT formalism, at different levels of theory, for two classes of representative compounds compiled from PubChem database, one comprising frequent hitters and the second one comprising rare hitters (biologically more selective compounds). We found that frequent hitters exert increased reactivity, mainly due to their electrophilic character, compared to the more selective class of compounds.
本研究的目标是通过经由反应性描述符估计的化学行为，来理解高通量筛选（HTS）结果中的生物混杂化合物（频繁命中化合物）。由于高通量筛选文库中的化合物缺乏生物选择性，化学反应性通常是一种不良特性。在本研究中，针对从PubChem数据库汇编的两类代表性化合物，在不同理论水平下于密度泛函理论（DFT）形式体系内计算了反应性指数，一类包含频繁命中化合物，另一类包含罕见命中化合物（生物选择性更强的化合物）。我们发现，与生物选择性更强的化合物类别相比，频繁命中化合物表现出更高的反应性，这主要归因于它们的亲电特性。
