HQSAR, CoMFA, CoMSIA Docking Studies and Simulation MD on Quinazolines/Quinolines Derivatives for DENV Virus Inhibitory Activity

Tabti, Kamal; Elmchichi, Larbi; Sbai, Abdelouahid; Maghat, Hamid; Bouachrine, Mohammed; Lakhlifi, Tahar

doi:10.1007/s42250-022-00484-4

Cited by 13 publications

(18 citation statements)

References 60 publications

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“…Quantitative structure‐activity relationship (QSAR) modeling is a valuable method for discovering the correlation between molecular structure and bioactivity, enabling the prediction of the activities of new molecules and facilitating the development of more active compounds [13,14] …”

Section: Introductionmentioning

confidence: 99%

“…Using the structural information generated by the QSAR models, we designed five new inhibitors that were more potent than the original compounds [24] . To strengthen the results of our models, we also conducted binding free energy calculations, molecular docking, and ADME/Tox studies [25,26] .…”

Section: Introductionmentioning

confidence: 99%

“…[24] To strengthen the results of our models, we also conducted binding free energy calculations, molecular docking, and ADME/Tox studies. [25,26] The ultimate objective of this study is to establish a theoretical foundation for identifying new colchicine binding site inhibitors based on 4-arylpiperazine-1-carbonyl-2H-1,2,3-triazole.…”

Section: Introductionmentioning

confidence: 99%

“…[17,18] Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) analysis can be used to evaluate the bioavailability and toxicity profile of molecules. [19,20] In this present study, we employed Gaussian field-based 3D-QSAR and atom-based 3D-QSAR with the PHASE module (2021 version, Schrödinger, LLC, NY) to analyze a series of triazole derivatives with cytotoxic activities. [21,22] To ensure statistical robustness, we performed internal validation on the developed models.…”

Section: Introductionmentioning

confidence: 99%

“…Molecular docking and dynamics are powerful approaches for understanding the structural interactions between binding molecules and protein targets, predicting the optimal binding form [17,18] . Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) analysis can be used to evaluate the bioavailability and toxicity profile of molecules [19,20] …”

Section: Introductionmentioning

confidence: 99%

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Computational Exploration of the Structural Requirements of Triazole Derivatives as Colchicine Binding Site Inhibitors

et al. 2023

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Colchicine inhibits microtubule assembly by preventing tubulin polymerization, making the colchicine binding site a promising target against cancer. The present study focuses on the 3D‐QSAR analysis of 31 triazole analogs. The atom‐based and field‐based QSAR models exhibit significant statistical results for internal and external validations, with the atom‐based 3D‐QSAR model showing a Q2 of 0.658 and R2 of 0.998, and the field‐based 3D‐QSAR model showing a Q2 of 0.658 and R2 of 0.998. The 3D‐QSAR atom‐based pharmacophore model explains biological activity using a six‐point hypothesis (AHHRRR.1), while the field‐based 3D‐QSAR model explains activity based on steric, electrostatic, hydrophobic, and hydrogen bond donor/acceptor fields. Based on the 3D contour maps generated, five new compounds were designed and their ADME/Tox properties predicted. The results suggested that these compounds possess potent pharmacological characteristics. The results of the molecular docking analysis showed that Pred01 and Pred02 had higher docking scores (−6.2417Kcal/mol and −6.5049Kcal/mol, respectively) than compound 15, and they formed notable hydrogen bonds and hydrophobic interactions with active site residues. The MMGBSA results confirmed these findings and emphasized the essential role of van der Waals energy in the binding energy. Moreover, the dynamic stability of the complexes was further supported by MD simulations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Computational Exploration of the Structural Requirements of Triazole Derivatives as Colchicine Binding Site Inhibitors

et al. 2023

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Quality Control of Coumarins, Furocoumarins and Polymethoxyflavones in Citrus Essential Oils: In Silico Analysis

Ouabane.,

Alaqarbeh,

Hajji

et al. 2024

ChemistrySelect

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Citrus essential oils (EOs) contain a variety of secondary metabolites, including coumarins (Cs), furocoumarins (FCs) and polymethoxyflavones (PMFs), all with different biological activities. While Regulation (EC) No 1334/2008 strictly regulates the use of coumarins, undesirable side effects of consuming furocoumarins remain without established maximum toxicity limits for human dietary intake. This study is based on an in‐silico approach aimed at determining these toxicity limits for the oxygenated heterocyclic compounds of citrus EOs approved for use in food. In addition, an innovative quantitative structure‐property relationship (QSPR) using the linear retention index system was explored to characterize the oxygenated heterocyclic compounds (COHs) present in these essential oils. Molecular docking of the studied compounds provided crucial insights into the structure‐odor relationships, offering insights into their mechanisms of action. In addition, an analysis of the pharmacokinetic and pharmacodynamic properties through ADME‐Tox deconstruction provides insight into the potential side effects of their consumption. The results are consolidated by dynamic simulations, providing crucial data for the development of regulations on the maximum toxicity limits of citrus EOs, given the health implications of the various compounds such as coumarins, furocoumarins and polymethoxyflavones present in these essential oils.

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Exploring Structure–Toxicity Relationships in Nitrobenzene and Derivatives: A Multifaceted Biochemical Investigation Using 3D–QSPR, HQSPR, Molecular Docking, and MD Simulation

Ouabane,

Zaki,

Alaqarbeh

et al. 2024

ChemistrySelect

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Nitrobenzene derivatives present an environmental concern to aquatic organisms, as well as a potential adverse effects on human health due to their toxicity. Therefore, monitoring nitrobenzene contamination levels is critical to protect both the ecosystem and the public. This study aims to quantitatively correlate the toxicity of nitrobenzene derivatives to their chemical structures using computational chemistry methods such as 3D‐QSPR, HQSPR, Molecular Docking and MD simulation. Additionally, to investigate the type of interactions and stability of nitrobenzene derivatives with the PP2 protein involved in the Phloem protein 2 (PP2). From each computational method a prediction model was extracted HQSPR (Atomic, Bonds, Donor/Acceptor, 3D‐QSPR (Steric, Electrostatic, Hydrophobic, Acceptor), and used for the design of X1 and X2 new nitrobenzene derivatives, which showed remarkable stability and better interactions. This study contributes to the understanding of the nitrobenzene derivatives’ toxicity and offers materials towards the understanding of the mechanism of action of these substances in protein–ligand interactions.

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HQSAR, CoMFA, CoMSIA Docking Studies and Simulation MD on Quinazolines/Quinolines Derivatives for DENV Virus Inhibitory Activity

Cited by 13 publications

References 60 publications

Computational Exploration of the Structural Requirements of Triazole Derivatives as Colchicine Binding Site Inhibitors

Computational Exploration of the Structural Requirements of Triazole Derivatives as Colchicine Binding Site Inhibitors

Quality Control of Coumarins, Furocoumarins and Polymethoxyflavones in Citrus Essential Oils: In Silico Analysis

Exploring Structure–Toxicity Relationships in Nitrobenzene and Derivatives: A Multifaceted Biochemical Investigation Using 3D–QSPR, HQSPR, Molecular Docking, and MD Simulation

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