Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types

Hadni, Hanine; Mazigh, Mohamed; El’mbarki, Charif; Bouayad, Asmae; Elhallaoui, Menana

doi:10.1155/2018/8639173

Cited by 26 publications

(23 citation statements)

References 19 publications

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“…Molecular docking was performed by using default settings of Maestro v‐11.4. Selected proteins 1J3K , 3QG2 , and 3QGT were auto‐downloaded via software under the specific organism P. falciparum . The expression system of E. coli was performed under systematic steps, as follows: default setting and flexible space of ligands were validated by comparison of biological activity, and GlideScore, docking parameter, and best docked ligands were fit into the cavities with lower energy score.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological andIn SilicoStudy of Fluorine‐Containing Quinoline Hybrid Thiosemicarbazide Analogues

Patel

Prajapati

et al. 2019

Journal of Heterocyclic Chem

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A novel series of fluorine‐containing quinoline hybrid thiosemicarbazide analogues (8a–8l) were synthesized and tested for their biological activities. The antibacterial results demonstrated that compounds 8d and 8l [minimal inhibitory concentration (MIC) 62.5 μg/mL] were shown to have higher biological activity than ampicillin against Escherichia coli. Compound 8b (MIC 25 μg/mL) was shown to have the highest activity than was ampicillin against Staphylococcus aureus. The antifungal results demonstrated that compound 8j (MIC 100 μg/mL) has shown good activity. Most of the targeted compounds have shown potent antimalarial activity. Compounds 8d (0.19 μg/mL), 8g (0.30 μg/mL), 8h (0.36 μg/mL), 8k (0.10 μg/mL), 8l (0.28 μg/mL), 8k (0.10 μg/mL), and 8l (0.28 μg/mL) have notable activity than does the reference drug quinine. Compounds 8d (0.27 μg/mL), 8g (0.30 μg/mL), and 8k (0.17 μg/mL) have shown excellent activity against chloroquine‐resistant strain. The MTT assay performed on peripheral blood lymphocyte cultures showed a high percentage of lymphocyte viability [8d (99.64), 8g (99.46), 8h (98.83), and 8k (99.51)] at a maximum dose (10 μg/mL), depicting no cytotoxicity of these compounds on human lymphocytes in vitro. A molecular docking study was performed on Pf‐DHFR‐TS inhibitor. A molecular dynamics study has shown compound 8g to have better affinity with protein. ADME‐Tox and pharmacophore study of synthesized compounds suggested prediction of active site.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological andIn SilicoStudy of Fluorine‐Containing Quinoline Hybrid Thiosemicarbazide Analogues

Patel

Prajapati

et al. 2019

Journal of Heterocyclic Chem

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“…The two compounds have the same radicals R1 and R2 but belong to different structural categories as it is detailed in paragraph 2.1. The reported study by Yuvanyama et al 33,10 has found the binding modes and has localized the active sites on both wild and mutant type of protein (Pf-DHFR). The study performed with a potent inhibitor 1,3,5-triazine derivative which is a preclinical molecule called WR99210.…”

Section: Docking Studiesmentioning

confidence: 99%

“…Herein, we report the molecular modeling of 4-anilinoquinoline-triazine derivatives 9 . In order to pursue, our ongoing research on molecular modeling of antimalarial activity 10 . We aim in this study to develop a predictive QSAR model, which will be used to analyze the antimalarial activity of a series of 41 hybrid 4-anilinoquinoline-triazine derivatives ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

QSAR and Molecular docking studies of 4-anilinoquinoline-triazine hybrids as pf-DHFR inhibitors

Hadni¹,

Mazigh²,

Hallaoui³

2019

Mediterr.J.Chem.,

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A quantitative structure-activity relationship (QSAR) investigation was performed towards 41 hybrids of 4-anilinoquinoline-triazines as potential antimalarial agents. The study was carried out using descendant multiple linear regression analyses (MLR), and artificial neural networks (ANN). Quantum chemical descriptors were calculated using DFT-B3LYP method, with the basis set 6-31G. The values obtained for the correlation coefficient of 0.87 and 0.92 by MLR and ANN, respectively, show a good predictive quality of the established model. In addition, the predicted model has been confirmed by several validation methods such as leave-one-out (LOO) cross-validation, Y-randomization, and external validation. The observed activity and the structural features of the studied molecules were further highlighted by molecular docking study on both wild and quadruple mutant type of pf-DHFR protein. Furthermore, the present work deals to study the binding modes and the key protein-ligand interactions. This methodology will be used to design new antimalarial drugs.

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“…azaaurone are very important therapeutic targets, as they show several biological activities including antimalarial activity [16,17]. TheTriazine derivative such as cycloguanil and chlorcycloguanil are already approved as antimalarial agents [18,19]. In this paper, we used the concept of hybrid molecules (T 14 -T 30), , in which two pharmacophores are linked together to increase their inhibitory activity against covid-19 [20].…”

Section: Introductionmentioning

confidence: 99%

In silico Discovery of anti-SARS-CoV-2 agents via docking screening and ADMET properties

Hadni¹,

Elhallaoui²

2020

Preprint

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Abstract The novel coronavirus (SARS-CoV-2) is the causative factor in the COVID-19 pandemic that infected more than 3 million people and the number of deaths continues to rise. There are currently no drugs or vaccines available to treat this disease, which is a serious global health problem. In this study, we performed molecular docking of heterocyclic molecules based on Quinoline, Triazine and Azaaurone, and to increase their inhibitory efficacy, we have used hybrid molecules linking two pharmacophores such as quinoline-oxalamide, quinoline-triazine and azaaurone-triazine. In order to accelerate the drug discovery process against this new SARS-CoV-2. Hydroxychloroquine and Azithromycin drugs showed anti-SARS-CoV-2 activity, which is why we have considered these drugs as a reference for other molecules. Most compounds showed high inhibitory activity against SARS-CoV-2, and promising results in ADMET properties and drug likeness. Thus, these compounds present excellent drug candidates. These results would be of great help in leading discovery and optimization for new drug against novel coronavirus.

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Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types

Cited by 26 publications

References 19 publications

Design, Synthesis, and Biological andIn SilicoStudy of Fluorine‐Containing Quinoline Hybrid Thiosemicarbazide Analogues

Design, Synthesis, and Biological andIn SilicoStudy of Fluorine‐Containing Quinoline Hybrid Thiosemicarbazide Analogues

QSAR and Molecular docking studies of 4-anilinoquinoline-triazine hybrids as pf-DHFR inhibitors

In silico Discovery of anti-SARS-CoV-2 agents via docking screening and ADMET properties

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