Investigating the role of thymol as a promising inhibitor of pyruvate dehydrogenase kinase 3 for targeted cancer therapy
Copyright © 2024 Elsevier B.V. All rights reserved..
Protein kinases have emerged as major contributors to various diseases. They are currently exploited as a potential target in drug discovery because they play crucial roles in cell signaling, growth, and regulation. Their dysregulation is associated with inflammatory disorders, cancer, and neurodegenerative diseases. Pyruvate dehydrogenase kinase 3 (PDK3) has become an attractive drug target in cancer therapeutics. In the present study, we investigated the effective role of thymol in PDK3 inhibition due to the high affinity predicted through molecular docking studies. Hence, to better understand this inhibition mechanism, we carried out a 100 ns molecular dynamics (MD) simulation to analyse the dynamics and stability of the PDK3-thymol complex. The PDK3-thymol complex was stable and energetically favourable, with many intramolecular hydrogen bond interactions in the PDK3-thymol complex. Enzyme inhibition assay showed significant inhibition of PDK3 by thymol, revealing potential inhibitory action of thymol towards PDK3 (IC50 = 2.66 μM). In summary, we established thymol as one of the potential inhibitors of PDK3, proposing promising therapeutic implications for severe diseases associated with PDK3 dysregulation. This study further advances our understanding of thymol's therapeutic capabilities and potential role in cancer treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:259 |
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| Enthalten in: |
International journal of biological macromolecules - 259(2024), Pt 2 vom: 15. Feb., Seite 129314 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jairajpuri, Deeba Shamim [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.02.2024 Date Revised 22.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2024.129314 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367024675 |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Protein kinases have emerged as major contributors to various diseases. They are currently exploited as a potential target in drug discovery because they play crucial roles in cell signaling, growth, and regulation. Their dysregulation is associated with inflammatory disorders, cancer, and neurodegenerative diseases. Pyruvate dehydrogenase kinase 3 (PDK3) has become an attractive drug target in cancer therapeutics. In the present study, we investigated the effective role of thymol in PDK3 inhibition due to the high affinity predicted through molecular docking studies. Hence, to better understand this inhibition mechanism, we carried out a 100 ns molecular dynamics (MD) simulation to analyse the dynamics and stability of the PDK3-thymol complex. The PDK3-thymol complex was stable and energetically favourable, with many intramolecular hydrogen bond interactions in the PDK3-thymol complex. Enzyme inhibition assay showed significant inhibition of PDK3 by thymol, revealing potential inhibitory action of thymol towards PDK3 (IC50 = 2.66 μM). In summary, we established thymol as one of the potential inhibitors of PDK3, proposing promising therapeutic implications for severe diseases associated with PDK3 dysregulation. This study further advances our understanding of thymol's therapeutic capabilities and potential role in cancer treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cancer therapeutics | |
| 650 | 4 | |a Drug discovery | |
| 650 | 4 | |a Enzyme inhibition assay | |
| 650 | 4 | |a Inflammatory disorders | |
| 650 | 4 | |a Molecular dynamics simulation | |
| 650 | 4 | |a Natural compounds | |
| 650 | 4 | |a Protein kinases | |
| 650 | 7 | |a Pyruvate Dehydrogenase Acetyl-Transferring Kinase |2 NLM | |
| 650 | 7 | |a Thymol |2 NLM | |
| 650 | 7 | |a 3J50XA376E |2 NLM | |
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| 700 | 1 | |a Khan, Shama |e verfasserin |4 aut | |
| 700 | 1 | |a Anwar, Saleha |e verfasserin |4 aut | |
| 700 | 1 | |a Hussain, Afzal |e verfasserin |4 aut | |
| 700 | 1 | |a Alajmi, Mohamed F |e verfasserin |4 aut | |
| 700 | 1 | |a Hassan, Imtaiyaz |e verfasserin |4 aut | |
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