Elucidation of escitalopram oxalate and related antidepressants as putative inhibitors of PTP4A3/PRL-3 protein in hepatocellular carcinoma : A multi-computational investigation
Copyright © 2024 Elsevier Ltd. All rights reserved..
Hepatocellular carcinoma (HCC) persists to be one of the most devastating and deadliest malignancies globally. Recent research into the molecular signaling networks entailed in many malignancies has given some prominent insights that can be leveraged to create molecular therapeutics for combating HCC. Therefore, in the current communication, an in-silico drug repurposing approach has been employed to target the function of PTP4A3/PRL-3 protein in HCC using antidepressants: Fluoxetine hydrochloride, Citalopram, Amitriptyline, Imipramine, and Escitalopram oxalate as the desired ligands. The density function theory (DFT) and chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters for the chosen ligands were evaluated to comprehend the pharmacokinetics, drug-likeness properties, and bioreactivity of the ligands. The precise interaction mechanism was explored using computational methods such as molecular docking and molecular dynamics (MD) simulation studies to assess the inhibitory effect and the stability of the interactions against the protein of interest. Escitalopram oxalate exhibited a comparatively significant docking score (-7.4 kcal/mol) compared to the control JMS-053 (-6.8 kcal/mol) against the PRL-3 protein. The 2D interaction plots exhibited an array of hydrophobic and hydrogen bond interactions. The findings of the ADMET forecast confirmed that it adheres to Lipinski's rule of five with no violations, and DFT analysis revealed a HOMO-LUMO energy gap of -0.26778 ev, demonstrating better reactivity than the control molecule. The docked complexes were subjected to MD studies (100 ns) showing stable interactions. Considering all the findings, it can be concluded that Escitalopram oxalate and related therapeutics can act as potential pharmacological candidates for targeting the activity of PTP4A3/PRL-3 in HCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:110 |
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| Enthalten in: |
Computational biology and chemistry - 110(2024) vom: 29. Feb., Seite 108039 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mir, Ishfaq Hassan [VerfasserIn] |
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| Links: |
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| Themen: |
Antidepressants |
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| Anmerkungen: |
Date Revised 12.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.compbiolchem.2024.108039 |
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NLM369610741 |
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| 245 | 1 | 0 | |a Elucidation of escitalopram oxalate and related antidepressants as putative inhibitors of PTP4A3/PRL-3 protein in hepatocellular carcinoma |b A multi-computational investigation |
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| 520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Hepatocellular carcinoma (HCC) persists to be one of the most devastating and deadliest malignancies globally. Recent research into the molecular signaling networks entailed in many malignancies has given some prominent insights that can be leveraged to create molecular therapeutics for combating HCC. Therefore, in the current communication, an in-silico drug repurposing approach has been employed to target the function of PTP4A3/PRL-3 protein in HCC using antidepressants: Fluoxetine hydrochloride, Citalopram, Amitriptyline, Imipramine, and Escitalopram oxalate as the desired ligands. The density function theory (DFT) and chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters for the chosen ligands were evaluated to comprehend the pharmacokinetics, drug-likeness properties, and bioreactivity of the ligands. The precise interaction mechanism was explored using computational methods such as molecular docking and molecular dynamics (MD) simulation studies to assess the inhibitory effect and the stability of the interactions against the protein of interest. Escitalopram oxalate exhibited a comparatively significant docking score (-7.4 kcal/mol) compared to the control JMS-053 (-6.8 kcal/mol) against the PRL-3 protein. The 2D interaction plots exhibited an array of hydrophobic and hydrogen bond interactions. The findings of the ADMET forecast confirmed that it adheres to Lipinski's rule of five with no violations, and DFT analysis revealed a HOMO-LUMO energy gap of -0.26778 ev, demonstrating better reactivity than the control molecule. The docked complexes were subjected to MD studies (100 ns) showing stable interactions. Considering all the findings, it can be concluded that Escitalopram oxalate and related therapeutics can act as potential pharmacological candidates for targeting the activity of PTP4A3/PRL-3 in HCC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antidepressants | |
| 650 | 4 | |a Drug repurposing | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Molecular docking | |
| 650 | 4 | |a Molecular dynamic simulations | |
| 650 | 4 | |a PTP4A3 | |
| 700 | 1 | |a Shyam, Kankipati Teja |e verfasserin |4 aut | |
| 700 | 1 | |a Balakrishnan, Susmida Seni |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Muthuvel Suresh |e verfasserin |4 aut | |
| 700 | 1 | |a Ramesh, Thiyagarajan |e verfasserin |4 aut | |
| 700 | 1 | |a Thirunavukkarasu, Chinnasamy |e verfasserin |4 aut | |
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