Exploring the biological promiscuity of high-throughput screening hits through DFT calculations |
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| Affiliation: | 1. Department of Computational Chemistry, Institute of Chemistry Timisoara of Romanian Academy, 24 Mihai Viteazul, Timisoara 300223, Romania;2. Quantum Organic Chemistry Group, Ruđer Bošković Institute, Bijenička cesta 54, Zagreb HR-10000, Croatia;3. Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA;1. University Department for Forensic Sciences, University of Split, Split, Croatia;2. Ruđer Bošković Institute, Zagreb, Croatia;3. Forensic Science Centre “Ivan Vučetić”, Zagreb, Croatia;4. Forensic Science Office, University of Zagreb, Zagreb, Croatia;5. Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia;1. College of Materials Science and Engineering, Chongqing University, Chongqing 400044, China;2. Pangang Group Panzhihua Steel and Vanagium Co., Ltd., Panzhihua 617000, Sichuan, China;1. Department of Geophysics, Universitas Padjadjaran, Jatinangor, Sumedang 45363, Indonesia;2. Nanotechnology and Graphene Research Center, Universitas Padjadjaran, Jatinangor, Sumedang 45363, Indonesia;3. Fachbereich Physik und Forschungszentrum OPTIMAS, Universität Kaiserslautern, Erwin-Schrödinger-Straße, D-67663 Kaiserslautern, Germany;1. Beijing Institute of Pharmacology & Toxicology, Beijing, China;2. Spedding Research Solutions, Le Vésinet, France;3. Centre for Cardiometabolic Health Research, Robert Gordon University, Aberdeen, UK;4. Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, France;5. Centre for Obesity Research & Education, Robert Gordon University, Aberdeen, UK;1. School of Computer Science and Technology, Beijing Institute of Technology, 100081 Beijing, China;2. Department of Computer Science and Technology, Tsinghua University, 100084 Beijing, China |
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| Abstract: | 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. |
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| Keywords: | Frequent hitters Biological promiscuity HTS Chemical reactivity descriptors DFT |
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