Docking-Guided 3D-QSAR Studies of 4-Aminoquinoline-1,3,5-triazines as Inhibitors for <i>Plasmodium falciparum</i> Dihydrofolate Reductase
Mutations in Plasmodium falciparum dihydrofolate reductase (PfDHFR), together with other mutations, hinder malaria elimination in Southeast Asia due to multiple drug resistance. In this article, molecular docking-guided three-dimensional (3D) quantitative structure-activity relationship (QSAR) analy...
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Department of Chemistry, Universitas Gadjah Mada
2020
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oai:doaj.org-article:183c4de5d13c4802827cf35dce4b5f742021-12-02T12:53:43ZDocking-Guided 3D-QSAR Studies of 4-Aminoquinoline-1,3,5-triazines as Inhibitors for <i>Plasmodium falciparum</i> Dihydrofolate Reductase1411-94202460-157810.22146/ijc.50674https://doaj.org/article/183c4de5d13c4802827cf35dce4b5f742020-05-01T00:00:00Zhttps://jurnal.ugm.ac.id/ijc/article/view/50674https://doaj.org/toc/1411-9420https://doaj.org/toc/2460-1578Mutations in Plasmodium falciparum dihydrofolate reductase (PfDHFR), together with other mutations, hinder malaria elimination in Southeast Asia due to multiple drug resistance. In this article, molecular docking-guided three-dimensional (3D) quantitative structure-activity relationship (QSAR) analysis of 4-aminoquinoline-1,3,5-triazines as inhibitors for the wild-type (WT) PfDHFR to identify the molecular determinants of the inhibitors binding are presented. Compounds 4-aminoquinoline-1,3,5-triazines were reported promising to be developed as the non-resistant drugs. The 3D-QSAR analysis resulted in the best model with the R2 and Q2 values of 0.881 and 0.773, respectively. By correlating the molecular interaction fields (MIFs) of the best model to the docking pose employed to guide the 3D-QSAR analysis, S108 residue of the WT-PfDHFR was unfortunately recognized as one of the molecular determinants. Since the S108 residue is one of the mutation points of the PfDHFR mutants, the subsequent design strategy should modify the morpholine moiety to avoid the interaction with the S108 residue of the WT-PfDHFR.Radite YogaswaraMaria Ludya PulungSri Hartati YulianiEnade Perdana IstyastonoDepartment of Chemistry, Universitas Gadjah Madaarticleplasmodium falciparum dihydrofolate reductase3d-qsarmolecular dockingmultiple drug resistanceChemistryQD1-999ENIndonesian Journal of Chemistry, Vol 20, Iss 6, Pp 1455-1460 (2020) |
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plasmodium falciparum dihydrofolate reductase 3d-qsar molecular docking multiple drug resistance Chemistry QD1-999 |
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plasmodium falciparum dihydrofolate reductase 3d-qsar molecular docking multiple drug resistance Chemistry QD1-999 Radite Yogaswara Maria Ludya Pulung Sri Hartati Yuliani Enade Perdana Istyastono Docking-Guided 3D-QSAR Studies of 4-Aminoquinoline-1,3,5-triazines as Inhibitors for <i>Plasmodium falciparum</i> Dihydrofolate Reductase |
description |
Mutations in Plasmodium falciparum dihydrofolate reductase (PfDHFR), together with other mutations, hinder malaria elimination in Southeast Asia due to multiple drug resistance. In this article, molecular docking-guided three-dimensional (3D) quantitative structure-activity relationship (QSAR) analysis of 4-aminoquinoline-1,3,5-triazines as inhibitors for the wild-type (WT) PfDHFR to identify the molecular determinants of the inhibitors binding are presented. Compounds 4-aminoquinoline-1,3,5-triazines were reported promising to be developed as the non-resistant drugs. The 3D-QSAR analysis resulted in the best model with the R2 and Q2 values of 0.881 and 0.773, respectively. By correlating the molecular interaction fields (MIFs) of the best model to the docking pose employed to guide the 3D-QSAR analysis, S108 residue of the WT-PfDHFR was unfortunately recognized as one of the molecular determinants. Since the S108 residue is one of the mutation points of the PfDHFR mutants, the subsequent design strategy should modify the morpholine moiety to avoid the interaction with the S108 residue of the WT-PfDHFR. |
format |
article |
author |
Radite Yogaswara Maria Ludya Pulung Sri Hartati Yuliani Enade Perdana Istyastono |
author_facet |
Radite Yogaswara Maria Ludya Pulung Sri Hartati Yuliani Enade Perdana Istyastono |
author_sort |
Radite Yogaswara |
title |
Docking-Guided 3D-QSAR Studies of 4-Aminoquinoline-1,3,5-triazines as Inhibitors for <i>Plasmodium falciparum</i> Dihydrofolate Reductase |
title_short |
Docking-Guided 3D-QSAR Studies of 4-Aminoquinoline-1,3,5-triazines as Inhibitors for <i>Plasmodium falciparum</i> Dihydrofolate Reductase |
title_full |
Docking-Guided 3D-QSAR Studies of 4-Aminoquinoline-1,3,5-triazines as Inhibitors for <i>Plasmodium falciparum</i> Dihydrofolate Reductase |
title_fullStr |
Docking-Guided 3D-QSAR Studies of 4-Aminoquinoline-1,3,5-triazines as Inhibitors for <i>Plasmodium falciparum</i> Dihydrofolate Reductase |
title_full_unstemmed |
Docking-Guided 3D-QSAR Studies of 4-Aminoquinoline-1,3,5-triazines as Inhibitors for <i>Plasmodium falciparum</i> Dihydrofolate Reductase |
title_sort |
docking-guided 3d-qsar studies of 4-aminoquinoline-1,3,5-triazines as inhibitors for <i>plasmodium falciparum</i> dihydrofolate reductase |
publisher |
Department of Chemistry, Universitas Gadjah Mada |
publishDate |
2020 |
url |
https://doaj.org/article/183c4de5d13c4802827cf35dce4b5f74 |
work_keys_str_mv |
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