Cargando…
Molecular docking and QSAR studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-DHFR
Plasmodium falciparum dihydrofolate reductase (pf-DHFR) is one of the several targets in the treatment of malaria. Double and quadruple mutations at residues 51, 59, 108, and 164 of pf-DHFR have been linked to antifolate resistance. Several efforts are underway to overcome this drug resistance and t...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717158/ https://www.ncbi.nlm.nih.gov/pubmed/31485537 http://dx.doi.org/10.1016/j.heliyon.2019.e02357 |
_version_ | 1783447508154843136 |
---|---|
author | Hadni, Hanine Elhallaoui, Menana |
author_facet | Hadni, Hanine Elhallaoui, Menana |
author_sort | Hadni, Hanine |
collection | PubMed |
description | Plasmodium falciparum dihydrofolate reductase (pf-DHFR) is one of the several targets in the treatment of malaria. Double and quadruple mutations at residues 51, 59, 108, and 164 of pf-DHFR have been linked to antifolate resistance. Several efforts are underway to overcome this drug resistance and to produce potential inhibitors. In this regard, the quantitative structure-activity relationship (QSAR) and docking studies were performed for previously reported 4-anilinoquinoline and 1,3,5-triazines based molecular hybrids. The generated model showed good correlation coefficients (R(2) = 0.70) and test set prediction coefficient (R(2) = 0.74). These outcomes showed the good predictive competence of the established QSAR model. Based on these results we docked into active site of pf-DHFR protein with the most active (4) and the less active (5) compounds. The docking results revealed that these molecules interact specifically with SER108 and ILE164 in the pf-DHFR binding pocket as that of best active compound but also showed additional interactions with LEU40 and GLY44. |
format | Online Article Text |
id | pubmed-6717158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-67171582019-09-04 Molecular docking and QSAR studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-DHFR Hadni, Hanine Elhallaoui, Menana Heliyon Article Plasmodium falciparum dihydrofolate reductase (pf-DHFR) is one of the several targets in the treatment of malaria. Double and quadruple mutations at residues 51, 59, 108, and 164 of pf-DHFR have been linked to antifolate resistance. Several efforts are underway to overcome this drug resistance and to produce potential inhibitors. In this regard, the quantitative structure-activity relationship (QSAR) and docking studies were performed for previously reported 4-anilinoquinoline and 1,3,5-triazines based molecular hybrids. The generated model showed good correlation coefficients (R(2) = 0.70) and test set prediction coefficient (R(2) = 0.74). These outcomes showed the good predictive competence of the established QSAR model. Based on these results we docked into active site of pf-DHFR protein with the most active (4) and the less active (5) compounds. The docking results revealed that these molecules interact specifically with SER108 and ILE164 in the pf-DHFR binding pocket as that of best active compound but also showed additional interactions with LEU40 and GLY44. Elsevier 2019-08-26 /pmc/articles/PMC6717158/ /pubmed/31485537 http://dx.doi.org/10.1016/j.heliyon.2019.e02357 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hadni, Hanine Elhallaoui, Menana Molecular docking and QSAR studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-DHFR |
title | Molecular docking and QSAR studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-DHFR |
title_full | Molecular docking and QSAR studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-DHFR |
title_fullStr | Molecular docking and QSAR studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-DHFR |
title_full_unstemmed | Molecular docking and QSAR studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-DHFR |
title_short | Molecular docking and QSAR studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-DHFR |
title_sort | molecular docking and qsar studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-dhfr |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717158/ https://www.ncbi.nlm.nih.gov/pubmed/31485537 http://dx.doi.org/10.1016/j.heliyon.2019.e02357 |
work_keys_str_mv | AT hadnihanine moleculardockingandqsarstudiesformodelingtheantimalarialactivityofhybrids4anilinoquinolinetriazinesderivativeswiththewildtypeandmutantreceptorpfdhfr AT elhallaouimenana moleculardockingandqsarstudiesformodelingtheantimalarialactivityofhybrids4anilinoquinolinetriazinesderivativeswiththewildtypeandmutantreceptorpfdhfr |