title: Exploring the biological promiscuity of high-throughput screening hits through DFT calculations.
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.
authors.affiliation: Department of Computational Chemistry, Institute of Chemistry Timisoara of Romanian Academy, 24 Mihai Viteazul, Timisoara 300223, Romania. Electronic address: rcurpan@acad-icht.tm.edu.ro.
authors.forename: Ramona
authors.initials: R
authors.lastname: Curpăn
authors.affiliation: Department of Computational Chemistry, Institute of Chemistry Timisoara of Romanian Academy, 24 Mihai Viteazul, Timisoara 300223, Romania.
authors.forename: Sorin
authors.initials: S
authors.lastname: Avram
authors.affiliation: Quantum Organic Chemistry Group, Ruđer Bošković Institute, Bijenička cesta 54, Zagreb HR-10000, Croatia.
authors.forename: Robert
authors.initials: R
authors.lastname: Vianello
authors.affiliation: Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Bologa
mesh_terms: D062126:Databases, Chemical; D057166:High-Throughput Screening Assays; D011789:Quantum Theory; D013816:Thermodynamics
keywords: Biological promiscuity; Chemical reactivity descriptors; DFT; Frequent hitters; HTS