title: A DFT-based QSAR study on inhibition of human dihydrofolate reductase.
abstract: Diaminopyrimidine derivatives are frequently used as inhibitors of human dihydrofolate reductase, for example in treatment of patients whose immune system are affected by human immunodeficiency virus. Forty-seven dicyclic and tricyclic potential inhibitors of human dihydrofolate reductase were analyzed using the quantitative structure-activity analysis supported by DFT-based and DRAGON-based descriptors. The developed model yielded an RMSE deviation of 1.1 a correlation coefficient of 0.81. The prediction set was characterized by R2=0.60 and RMSE=3.59. Factors responsible for inhibition process were identified and discussed. The resulting model was validated via cross validation and Y-scrambling procedure. From the best model, we found several mass-related descriptors and Sanderson electronegativity-related descriptors that have the best correlations with the investigated inhibitory concentration. These descriptors reflect results from QSAR studies based on characteristics of human dihydrofolate reductase inhibitors.
authors.affiliation: Department of Chemistry, Faculty of Science and Literature, Balikesir University, Balikesir 10145, Turkey. Electronic address: sedat@icnanotox.org.
authors.forename: Sedat
authors.initials: S
authors.lastname: Karabulut
authors.affiliation: Interdisciplinary Center for Nanotoxicity, Department of Chemistry and Biochemistry, Jackson State University, Jackson, 39217-0510 MS, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sizochenko
authors.affiliation: School of Medicine, Department of Obstetrics and Gynaecology, Uludag University, Gorukle Kampusu, Bursa 16120, Turkey.
authors.forename: Adnan
authors.initials: A
authors.lastname: Orhan
authors.affiliation: Interdisciplinary Center for Nanotoxicity, Department of Chemistry and Biochemistry, Jackson State University, Jackson, 39217-0510 MS, USA.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Leszczynski
mesh_terms: D005493:Folic Acid Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D025341:Principal Component Analysis; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory; D055672:Static Electricity; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase
keywords: DFT; Descriptors; Diaminopyrimidine; Dihydrofolate reductase; QSAR; QSARins