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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Autores principales: Radite Yogaswara, Maria Ludya Pulung, Sri Hartati Yuliani, Enade Perdana Istyastono
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Publicado: Department of Chemistry, Universitas Gadjah Mada 2020
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic plasmodium falciparum dihydrofolate reductase
3d-qsar
molecular docking
multiple drug resistance
Chemistry
QD1-999
spellingShingle 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
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AT marialudyapulung dockingguided3dqsarstudiesof4aminoquinoline135triazinesasinhibitorsforiplasmodiumfalciparumidihydrofolatereductase
AT srihartatiyuliani dockingguided3dqsarstudiesof4aminoquinoline135triazinesasinhibitorsforiplasmodiumfalciparumidihydrofolatereductase
AT enadeperdanaistyastono dockingguided3dqsarstudiesof4aminoquinoline135triazinesasinhibitorsforiplasmodiumfalciparumidihydrofolatereductase
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