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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hadni, Hanine, Elhallaoui, Menana
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