Identification of acridinedione scaffolds as potential inhibitor of DENV‐2 C protein: An in silico strategy to combat dengue

Kumar, Sachin; Bhardwaj, Vijay Kumar; Singh, Rahul; Das, Pralay; Purohit, Rituraj

doi:10.1002/jcb.30237

Cited by 58 publications

(45 citation statements)

References 46 publications

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“…The binding free energy from MM‐PBSA computations provides a semiquantitative measure of inhibitor affinity with protein 53 . The binding free energy of reference and selected quinoline molecules with MEK1 and ATP were tabulated in Supporting Information: Tables S2 and S3.…”

Section: Resultsmentioning

confidence: 99%

Computational targeting of allosteric site of MEK1 by quinoline‐based molecules

Singh

Bhardwaj

Purohit

2022

Cell Biochemistry & Function

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MEK1 is an attractive target due to its role in selective extracellular‐signal‐regulated kinase phosphorylation, which plays a pivotal role in regulating cell proliferation. Another benefit of targeting the MEK protein is its unique hydrophobic pocket that can accommodate highly selective allosteric inhibitors. To date, various MEK1 inhibitors have reached clinical trials against several cancers, but they were discarded due to their severe toxicity and low efficacy. Thus, the development of allosteric inhibitors for MEK1 is the demand of the hour. In this in‐silico study, molecular docking, long‐term molecular dynamics (5 µs), and molecular mechanics Poisson–Boltzmann surface area analysis were undertaken to address the potential of quinolines as allosteric inhibitors. We selected four reference MEK1 inhibitors for the comparative analysis. The drug‐likeness and toxicity of these molecules were also examined based on their ADMET and Toxicity Prediction by Komputer Assisted Technology profiles. The outcome of the analysis revealed that the quinolines (4m, 4o, 4s, and 4n) exhibited better stability and binding affinity while being nontoxic compared to reference inhibitors. We have reached the conclusion that these quinoline molecules could be checked by experimental studies to validate their use as allosteric inhibitors against MEK1.

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Section: Resultsmentioning

confidence: 99%

Computational targeting of allosteric site of MEK1 by quinoline‐based molecules

Singh

Bhardwaj

Purohit

2022

Cell Biochemistry & Function

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“…Further, molecular docking and MD simulation analysis were performed to investigate the mode of interaction and dynamics of complexation. 59…”

Section: Introductionmentioning

confidence: 99%

Investigating binding mechanism of thymoquinone to human transferrin, targeting Alzheimer's disease therapy

Xue

DasGupta

Alam

et al. 2022

J of Cellular Biochemistry

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Iron deposition in the central nervous system (CNS) is one of the causes of neurodegenerative diseases. Human transferrin (hTf) acts as an iron carrier present in the blood plasma, preventing it from contributing to redox reactions. Plant compounds and their derivatives are frequently being used in preventing or delaying Alzheimer's disease (AD). Thymoquinone (TQ), a natural product has gained popularity because of its broad therapeutic applications. TQ is one of the significant phytoconstituent of Nigella sativa. The binding of TQ to hTf was determined by spectroscopic methods and isothermal titration calorimetry. We have observed that TQ strongly binds to hTf with a binding constant (K) of 0.22 × 106 M−1 and forming a stable complex. In addition, isothermal titration calorimetry revealed the spontaneous binding of TQ with hTf. Molecular docking analysis showed key residues of the hTf that were involved in the binding to TQ. We further performed a 250 ns molecular dynamics simulation which deciphered the dynamics and stability of the hTf‐TQ complex. Structure analysis suggested that the binding of TQ doesn't cause any significant alterations in the hTf structure during the course of simulation and a stable complex is formed. Altogether, we have elucidated the mechanism of binding of TQ with hTf, which can be further implicated in the development of a novel strategy for AD therapy.

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“…Additionally, the other in silico techniques, such as molecular dynamics simulation, molecular mechanics/ generalized Born surface area model (MM/GBSA), and molecular force field/Poisson Boltzmann surface area model (MM/PBSA), can be used to screen inhibitors of key targets related to hepatoma. These technological methods have been widely used in the screening of key target protein inhibitors or agonists of related diseases in the natural product library of TCM [30][31][32]. They will play a role in promoting the modern research of TCM and the screening of new drug targets in the future.…”

Section: Introductionmentioning

confidence: 99%

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis

Wang

et al. 2022

BioMed Research International

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Hepatoma is one of the most common malignant tumors. The incidence rate is high in developing countries, and China has the most significant number of cases. Dahuang is a classic traditional antitumor drug commonly used in China and has also been applied to treat hepatoma. However, the potential mechanism of Dahuang in treating hepatoma is not clear. Therefore, this study is aimed at elucidating the possible molecular mechanism and key targets of Dahuang using methods of network pharmacology, molecular docking, and survival analysis. Firstly, the active ingredients and key targets of Dahuang were analyzed through public databases, and then the drug-ingredient-target-disease network diagram of Dahuang against hepatoma was constructed. Five main active components and five core targets were determined according to the enrichment degree. Enrichment analysis demonstrated that Dahuang treated hepatoma through the multiple pathways in cancer. Additionally, molecular docking predicted that aloe-emodin and PIK3CG depicted the best binding energy. Survival analysis indicated that a high/ESR1 gene expression had a relatively good prognosis for patients with hepatoma ( p < 0.05 ). In conclusion, the current study results demonstrated that Dahuang could treat hepatoma through a variety of active ingredients, targets, and multiantitumor pathways. Moreover, it effectively improved the prognosis of hepatoma patients. ESR1 is the potential key gene that is beneficial for the survival of hepatoma patients. Also, aloe-emodin and beta-sitosterol are the two main active crucial ingredients for hepatoma treatment. The study also provided some functional bases and references for the development of new drugs, target mining, and experimental animal research of hepatoma in the future.

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Identification of acridinedione scaffolds as potential inhibitor of DENV‐2 C protein: An in silico strategy to combat dengue

Cited by 58 publications

References 46 publications

Computational targeting of allosteric site of MEK1 by quinoline‐based molecules

Computational targeting of allosteric site of MEK1 by quinoline‐based molecules

Investigating binding mechanism of thymoquinone to human transferrin, targeting Alzheimer's disease therapy

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis

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