QSAR and molecular docking studies of 1,3-dioxoisoindoline-4-aminoquinolines as potent antiplasmodium hybrid compounds
Quantitative structure–activity relationships (QSAR) provides a model that link biological activities of compounds to thier chemical stuctures and molecular docking study reveals the interaction between drug and its target enzyme. These studies were conducted on 1,3-dioxoisoindoline-4-aminoquinoline...
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doaj-6a031fb2998e454d86bf793c1d3c8a4f2020-11-25T02:04:55ZengElsevierHeliyon2405-84402020-03-0163e03449QSAR and molecular docking studies of 1,3-dioxoisoindoline-4-aminoquinolines as potent antiplasmodium hybrid compoundsAliyu Wappah Mahmud0Gideon Adamu Shallangwa1Adamu Uzairu2Department of Applied Chemistry, Kaduna Polytechnic, Kaduna, Nigeria; Corresponding author.Chemistry Department, Ahmadu Bello University, Zaria, NigeriaChemistry Department, Ahmadu Bello University, Zaria, NigeriaQuantitative structure–activity relationships (QSAR) provides a model that link biological activities of compounds to thier chemical stuctures and molecular docking study reveals the interaction between drug and its target enzyme. These studies were conducted on 1,3-dioxoisoindoline-4-aminoquinolines with the aim of producing a model that could be used to design highly potent antiplasmodium. The compounds were first optimized using Density Functional Theory (DFT) with basis set B3LYP/6-31G∗ then their descriptors calculated. Genetic Function Algorithm (GFA) was used to select descriptors and build the model. One of the four models generated was found to be the best having internal and external squared correlation coefficient (R2) of 0.9459 and 0.7015 respectively, adjusted squared correlation coefficient (Radj) of 0.9278, leave-one-out (LOO) cross-validation coefficient (Q2cv) of 0.8882. The model shows that antiplasmodial activities of 1,3-dioxoisoindoline-4-aminoquinolines depend on ATSC5i, GATS8p, minHBint3, minHBint5, MLFER_A and topoShape descriptors. The model was validated to be predictive, robust and reliable. Hence, it can predict the antiplasmodium activities of new 1,3-dioxoisoindoline-4-aminoquinolines.The docking result indicates strong binding between 1,3-dioxoisoindoline-4-aminoquinolines and Plasmodium falciparum lactate dehydrogenase (pfLDH), and revealed the important of the morpholinyl substituent and amide linker in inhibiting pfLDH. These results could serve as a model for designing novel 1,3-dioxoisoindoline-4-aminoquinolines as inhibitors of PfLDH with higher antiplasmodial activities.http://www.sciencedirect.com/science/article/pii/S2405844020302942Physical chemistryTheoretical chemistryPharmaceutical chemistryAntiplasmodiumQSARMolecular docking |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aliyu Wappah Mahmud Gideon Adamu Shallangwa Adamu Uzairu |
spellingShingle |
Aliyu Wappah Mahmud Gideon Adamu Shallangwa Adamu Uzairu QSAR and molecular docking studies of 1,3-dioxoisoindoline-4-aminoquinolines as potent antiplasmodium hybrid compounds Heliyon Physical chemistry Theoretical chemistry Pharmaceutical chemistry Antiplasmodium QSAR Molecular docking |
author_facet |
Aliyu Wappah Mahmud Gideon Adamu Shallangwa Adamu Uzairu |
author_sort |
Aliyu Wappah Mahmud |
title |
QSAR and molecular docking studies of 1,3-dioxoisoindoline-4-aminoquinolines as potent antiplasmodium hybrid compounds |
title_short |
QSAR and molecular docking studies of 1,3-dioxoisoindoline-4-aminoquinolines as potent antiplasmodium hybrid compounds |
title_full |
QSAR and molecular docking studies of 1,3-dioxoisoindoline-4-aminoquinolines as potent antiplasmodium hybrid compounds |
title_fullStr |
QSAR and molecular docking studies of 1,3-dioxoisoindoline-4-aminoquinolines as potent antiplasmodium hybrid compounds |
title_full_unstemmed |
QSAR and molecular docking studies of 1,3-dioxoisoindoline-4-aminoquinolines as potent antiplasmodium hybrid compounds |
title_sort |
qsar and molecular docking studies of 1,3-dioxoisoindoline-4-aminoquinolines as potent antiplasmodium hybrid compounds |
publisher |
Elsevier |
series |
Heliyon |
issn |
2405-8440 |
publishDate |
2020-03-01 |
description |
Quantitative structure–activity relationships (QSAR) provides a model that link biological activities of compounds to thier chemical stuctures and molecular docking study reveals the interaction between drug and its target enzyme. These studies were conducted on 1,3-dioxoisoindoline-4-aminoquinolines with the aim of producing a model that could be used to design highly potent antiplasmodium. The compounds were first optimized using Density Functional Theory (DFT) with basis set B3LYP/6-31G∗ then their descriptors calculated. Genetic Function Algorithm (GFA) was used to select descriptors and build the model. One of the four models generated was found to be the best having internal and external squared correlation coefficient (R2) of 0.9459 and 0.7015 respectively, adjusted squared correlation coefficient (Radj) of 0.9278, leave-one-out (LOO) cross-validation coefficient (Q2cv) of 0.8882. The model shows that antiplasmodial activities of 1,3-dioxoisoindoline-4-aminoquinolines depend on ATSC5i, GATS8p, minHBint3, minHBint5, MLFER_A and topoShape descriptors. The model was validated to be predictive, robust and reliable. Hence, it can predict the antiplasmodium activities of new 1,3-dioxoisoindoline-4-aminoquinolines.The docking result indicates strong binding between 1,3-dioxoisoindoline-4-aminoquinolines and Plasmodium falciparum lactate dehydrogenase (pfLDH), and revealed the important of the morpholinyl substituent and amide linker in inhibiting pfLDH. These results could serve as a model for designing novel 1,3-dioxoisoindoline-4-aminoquinolines as inhibitors of PfLDH with higher antiplasmodial activities. |
topic |
Physical chemistry Theoretical chemistry Pharmaceutical chemistry Antiplasmodium QSAR Molecular docking |
url |
http://www.sciencedirect.com/science/article/pii/S2405844020302942 |
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