Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual-acting compounds against SARS-CoV-2 Mpro and RdRp

Mermer, Arif; Vakal, Serhii

doi:10.29228/jrp.92

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…In contrast to the others, compound 5 violates one of Lipinski's rules because it has more than ten hydrogen bond acceptors. Compounds that fulfill Lipinski's criteria have the opportunity to be developed as oral drug candidates and have an impact on increasing the bioavailability of these compounds [33].…”

Section: Adme Resultsmentioning

confidence: 99%

Docking-based workflow and ADME prediction of some compounds in Curcuma longa and Andrographis paniculata as polymerase PA-PB1 inhibitors of influenza A/H5N1 virus

CITRA¹,

ARFAN²,

ALROEM³

et al. 2023

jrp

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Influenza is an infectious disease of the respiratory system caused by the influenza virus. Influenza virus RNA polymerase (RdRp) is essential in viral RNA replication and transcription. This polymerase has acid polymerase (PA) and polymerase basic 1 (PB1) subunits responsible for viral endonuclease and proteolytic activity. This study aims to determine the potential and interactions of the biochemical constituents of turmeric (Curcuma longa) and bitter (Andrographis paniculata) against the polymerase PA-PB1 (PDB ID: 3CM8) from the influenza A virus. The study was carried out using the molecular docking workflow method with a combination of standard-precision (SP), extraprecision (XP), and induced fit docking (IFD) utilizing the Maestro's Schrodinger. The docking result successfully identified seven compounds in C. longa and thirty-four in A. paniculata, which had a better docking score than R151785 as a reference ligand. XP docking showed compounds 1 from C. longa with a score of -7.555 kcal/mol and 4 from A. paniculata with a score of -9.156 kcal/mol. The IFD method results identified compounds 3 from C. longa and 5 from A. paniculata as potential compounds in inhibiting the activity of the polymerase PA-PB1 with a docking score of -9.979 kcal/mol, and -13.153 kcal/mol, respectively. All the best compounds interacted with critical residues such as Thr7,

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Section: Adme Resultsmentioning

confidence: 99%

Docking-based workflow and ADME prediction of some compounds in Curcuma longa and Andrographis paniculata as polymerase PA-PB1 inhibitors of influenza A/H5N1 virus

CITRA¹,

ARFAN²,

ALROEM³

et al. 2023

jrp

View full text Add to dashboard Cite

show abstract

“…On the other hand, although simulation techniques exist that are more accurate than molecular docking to perform free energy calculations [ 47 ], applying them in the present case (i.e., for such a large number of ligands) is impractical. Simpler methods, based on molecular mechanics and generalized Born surface area (MM/GBSA), were previously employed to assess the binding of ligands to CYP1A2 in a number of cases [ 48 , 49 , 50 , 51 , 52 ]. However, binding energies calculated by these methods resulted in predicted binding energies in the low femtomolar range, or sometimes even more favorable.…”

Section: Resultsmentioning

confidence: 99%

Dissecting CYP1A2 Activation by Arylalkanoic Acid Prodrugs toward the Development of Anti-Inflammatory Agents

Occhiuzzi,

Ioele,

De Luca

et al. 2023

IJMS

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Arylalkane-derived prodrugs of arylacetic acids are a small group of substances that have long been known for their anti-inflammatory action. Despite their ease of synthesis and good potential for the development of new potent and safe anti-inflammatory agents, this group of substances has not received much attention from researchers so far. Therefore, representative arylalkane derivatives were investigated through molecular docking techniques to verify the possible hepatic activation mode toward active metabolites by CYP1A2. In this regard, arylalkanoic acid prodrugs were docked with a crystallographic structure of human CYP1A2, in which the enzyme is co-crystallized with the selective competitive inhibitor α-naphthoflavone BHF. Of note, all the examined compounds proved capable of interacting with the enzyme active site in a manner similar to Nabumetone, thus confirming that a productive metabolic transformation is feasible. On the basis of these findings, it is possible to argue that subtle differences in the way CYP1A2 accommodates the ligands depend on the fine details of their molecular structures. Overall, these data suggest that compounds simply formed by an aromatic moiety bearing an appropriate alkane-derived chain could lead to innovative anti-inflammatory agents.

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“…This tool aided in forecasting ADME parameters and drug likeness for selected candidates, encompassing GI absorption, BBB Barrier, P-gp substrate, CTY1A2 inhibitor, and CYP2C9 inhibitor. These predictions are invaluable in assisting drug discovery efforts for one or multiple small molecules (38).…”

Section: Admet Sarmentioning

confidence: 99%

Omics Based Screening of novel inhibitors against malignant pleural mesothelioma

Saleem,

Waqas,

Ahmad

et al. 2024

Preprint

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Malignant pleural mesothelioma (MPM) is an aggressive cancer affecting the pleural membrane. It is characterized by its rarity and lethality, presenting limited treatment avenues. Vascular endothelial growth factor A (VEGF-A) is a crucial signaling protein that binds to and activates the VEGFR-2 (vascular endothelial growth factor receptor-2). This interaction initiates a signaling cascade promoting endothelial cell proliferation and migration, fostering the formation of new blood vessels and fueling tumor growth. In this study, immunogenic approaches were employed to predict potential antigenic epitopes targeting the VEGFR-2 receptor. These epitopes were utilized to construct a multi-epitope peptide, which was subsequently docked against VEGFR-2 receptors to assess binding capabilities and interactions. Three optimal epitopes from the vaccine construct were selected based on binding interactions. Peptides derived from these epitopes were then predicted and docked with VEGFR-2 receptors to analyze their binding abilities and interactions further. Moreover, three distinct datasets for MPM were selected, each representing a different condition: a normal dataset, a diseased dataset, and a dataset from treated individuals (using K-975 - Kirin). Common genes across these datasets were identified through Next-Generation Sequencing (NGS) analysis conducted on an online Galaxy server. Additionally, upregulated genes in malignant pleural mesothelioma were detected through NGS analysis, with sulf-1 identified as an upregulated gene protein. Molecular docking analysis against a phytochemical library was performed using sulf-1, leading to the selection of novel drugs acting as inhibitors against malignant pleural mesothelioma. Furthermore, the pharmacokinetic properties of selected compounds were analyzed. This study aims to screen potential inhibitors targeting VEGFA, block the VEGFR-2 receptor using immunogenic and non-toxic peptides derived from VEGFA, and identify differentially expressed genes in malignant mesothelioma through RNA sequencing for virtual screening of potential inhibitors.

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Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual-acting compounds against SARS-CoV-2 Mpro and RdRp

Cited by 4 publications

References 37 publications

Docking-based workflow and ADME prediction of some compounds in Curcuma longa and Andrographis paniculata as polymerase PA-PB1 inhibitors of influenza A/H5N1 virus

Docking-based workflow and ADME prediction of some compounds in Curcuma longa and Andrographis paniculata as polymerase PA-PB1 inhibitors of influenza A/H5N1 virus

Dissecting CYP1A2 Activation by Arylalkanoic Acid Prodrugs toward the Development of Anti-Inflammatory Agents

Omics Based Screening of novel inhibitors against malignant pleural mesothelioma

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