Karabulut, SedatSizochenko, NataliaLeszczynski, Jerzy2022-11-212022-11-212016-09-05Karabulut, S. vd. (2016). "A DFT-based QSAR study on inhibition of human dihydrofolate reductase". Journal of Molecular Graphics and Modelling, 70, 23-29.1093-32631873-4243https://doi.org/10.1016/j.jmgm.2016.09.005https://www.sciencedirect.com/science/article/pii/S109332631630170Xhttp://hdl.handle.net/11452/29513Diaminopyrimidine 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 R-2 = 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.eninfo:eu-repo/semantics/openAccessBiochemistry & molecular biologyComputer scienceCrystallographyMathematical & computational biologyDihydrofolate reductaseDiaminopyrimidineDFTDescriptorsQSARQSARinsNeural-networksPneumocystis-cariniiPotent inhibitorsDerivativesTriazinesAnalogsComplexFutureModelChemical bondsElectronegativityPatient treatmentVirusesComputational chemistryFolic Acid AntagonistsHumansInhibitory concentration 50Models, molecularPrincipal component analysisQuantitative structure-activity relationshipQuantum theoryStatic electricityTetrahydrofolate dehydrogenaseThermodynamicsArticle0003906257000042-s2.0-8498786186223297027649548Biochemical research methodsBiochemistry & molecular biologyComputer science, interdisciplinary applicationsCrystallographyMathematical & computational biologyFolic Acid Antagonists; Dihydrofolate Reductase; Mycobacterium Tuberculosis5 chloro 6 [[(2,5 dimethoxyphenyl)amino]methyl]quinazoline 2,4 diamine5 chloro n 6 (2,5 dimethoxybenzyl)quinazoline 2,4,6 triamine5 chloro n 6 (3,4,5 trimethoxybenzyl)quinazoline 2,4,6 triamine5 ethoxyquinazoline 2,4 diamine5 methoxyquinazoline 2,4 diamine6 (10H phenothiazin 10 ylmethyl)pteridine 2,4 diamine6 (10H phenoxazin 10 ylmethyl)pteridine 2,4 diamine6 (2 methoxybenzyl) 5,6,7,8 tetrahydroquinazoline 2,4 diamine6 (2 methylbenzyl) 5,6,7,8 tetrahydroquinazoline 2,4 diamine6 (3 thienylmethyl) 5,6,7,8 tetrahydroquinazoline 2,4 diamine6 (3,4 dichlorobenzyl) 5,6,7,8 tetrahydroquinazoline 2,4 diamine6 (5H dibenzo[b,f]azepin 5 ylmethyl)pyrido[2,3 d]pyrimidine 2,4 diamine6 (acridin 10(9H) ylmethyl)pteridine 2,4 diamine6 ethyl 5,6,7,8 tetrahydroquinazoline 2,4 diamine6 tert butyl 5,6,7,8 tetrahydroquinazoline 2,4 diamine6 [[(3 chlorophenyl)(methyl)amino]methyl]pyrido[3,2 d]pyrimidine 2,4 diamine6 [[(3,4 dichlorophenyl)(methyl)amino]methyl]pyrido[3,2 d]pyrimidine 2,4 diamine6 [[(4 chlorophenyl)(methyl)amino]methyl]pyrido[3,2 d]pyrimidine 2,4 diamine6 [[methyl(3,4,5 trimethoxyphenyl)amino]methyl]pyrido[3,2 d]pyrimidine 2,4 diamine6,7 bis(3,4 dichlorobenzyl)pteridine 2,4 diamine9 chlorobenzo[f]quinazoline 1,3 diamine9 methoxybenzo[f]quinazoline 1,3 diamineDihydrofolate reductase inhibitorPyrimidine derivativeUnclassified drugUnindexed drugDihydrofolate reductaseFolic acid antagonistArticleChemical structureDensity functional theoryElectrophilicityEnzyme active siteEnzyme inhibitionHumanInhibitory concentrationNucleophilicityPriority journalQuantitative structure activity relationChemistryIC50MetabolismMolecular modelPrincipal component analysisQuantum theoryStatic electricityThermodynamics