Natural Anthraquinones as Potential Akt1-Targeted Anticancer Agents
Background: The phosphoinositide 3-kinase/protein kinase B (Akt)/mammalian target of the rapamycin signaling pathway is crucial in cancer progression. Akt1, a vital pathway component, has emerged as a promising therapeutic target. Objectives: This study used molecular docking analysis to investig...
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| Format: | Article |
| Language: | English |
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Hamadan University of Medical Sciences
2024-12-01
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| Series: | Avicenna Journal of Medical Biochemistry |
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| Online Access: | https://ajmb.umsha.ac.ir/PDF/ajmb-12-123.pdf |
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| _version_ | 1850040367731179520 |
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| author | Shokoofeh Jamshidi Fatemeh Mahfouzi Setareh Shojaei Amir Taherkhani |
| author_facet | Shokoofeh Jamshidi Fatemeh Mahfouzi Setareh Shojaei Amir Taherkhani |
| author_sort | Shokoofeh Jamshidi |
| collection | DOAJ |
| description | Background: The phosphoinositide 3-kinase/protein kinase B (Akt)/mammalian target of the rapamycin signaling pathway is crucial in cancer progression. Akt1, a vital pathway component, has emerged as a promising therapeutic target.
Objectives: This study used molecular docking analysis to investigate the potential of anthraquinones (AQs) as Akt1 inhibitors.
Methods: The crystallographic structure of Akt1 was obtained from the Protein Data Bank (PDB ID: 4GV1). Twenty-one AQ compounds were selected for docking analyses using AutoDock 4.0. Binding affinities and interaction modes were compared with two Akt1 reference inhibitors.
Results: Eleven AQs demonstrated substantial binding affinity to the Akt1’s catalytic site at nanomolar concentrations. Hypericin and sennidin B exhibited the most potent inhibitory effects, with ΔGbinding values of -11.19 kcal/mol and -10.36 kcal /mol, respectively, surpassing control inhibitors. Hypericin formed three hydrogen bonds and two hydrophobic interactions with the Akt1 catalytic cleft, while sennidin B formed six hydrogen and one hydrophobic interaction.
Conclusion: This study identified several AQs, particularly hypericin and sennidin B, as promising Akt1 inhibitors with superior binding affinities compared to reference compounds. These findings provide a foundation for further developing AQ-based Akt1-targeted therapeutics in cancer treatment. Future research should focus on the in vitro and in vivo validation of these compounds’ efficacy and safety profiles. |
| format | Article |
| id | doaj-art-e9757247c4fa4dd58ae4c15f43c30f06 |
| institution | DOAJ |
| issn | 2345-4113 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Hamadan University of Medical Sciences |
| record_format | Article |
| series | Avicenna Journal of Medical Biochemistry |
| spelling | doaj-art-e9757247c4fa4dd58ae4c15f43c30f062025-08-20T02:56:06ZengHamadan University of Medical SciencesAvicenna Journal of Medical Biochemistry2345-41132024-12-0112212313010.34172/ajmb.2567Natural Anthraquinones as Potential Akt1-Targeted Anticancer AgentsShokoofeh Jamshidi0https://orcid.org/0000-0002-0646-1882Fatemeh Mahfouzi1https://orcid.org/0009-0005-7939-6048Setareh Shojaei2https://orcid.org/0000-0001-8323-1231Amir Taherkhani 3https://orcid.org/0000-0002-6546-8785Department of Oral and Maxillofacial Pathology, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Oral and Maxillofacial Pathology, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Oral and Maxillofacial Pathology, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, IranResearch Center for Molecular Medicine, Institute of Cancer, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, IranBackground: The phosphoinositide 3-kinase/protein kinase B (Akt)/mammalian target of the rapamycin signaling pathway is crucial in cancer progression. Akt1, a vital pathway component, has emerged as a promising therapeutic target. Objectives: This study used molecular docking analysis to investigate the potential of anthraquinones (AQs) as Akt1 inhibitors. Methods: The crystallographic structure of Akt1 was obtained from the Protein Data Bank (PDB ID: 4GV1). Twenty-one AQ compounds were selected for docking analyses using AutoDock 4.0. Binding affinities and interaction modes were compared with two Akt1 reference inhibitors. Results: Eleven AQs demonstrated substantial binding affinity to the Akt1’s catalytic site at nanomolar concentrations. Hypericin and sennidin B exhibited the most potent inhibitory effects, with ΔGbinding values of -11.19 kcal/mol and -10.36 kcal /mol, respectively, surpassing control inhibitors. Hypericin formed three hydrogen bonds and two hydrophobic interactions with the Akt1 catalytic cleft, while sennidin B formed six hydrogen and one hydrophobic interaction. Conclusion: This study identified several AQs, particularly hypericin and sennidin B, as promising Akt1 inhibitors with superior binding affinities compared to reference compounds. These findings provide a foundation for further developing AQ-based Akt1-targeted therapeutics in cancer treatment. Future research should focus on the in vitro and in vivo validation of these compounds’ efficacy and safety profiles.https://ajmb.umsha.ac.ir/PDF/ajmb-12-123.pdfakt1anthraquinonecancerdrugmolecular dockingtraditional medicine |
| spellingShingle | Shokoofeh Jamshidi Fatemeh Mahfouzi Setareh Shojaei Amir Taherkhani Natural Anthraquinones as Potential Akt1-Targeted Anticancer Agents Avicenna Journal of Medical Biochemistry akt1 anthraquinone cancer drug molecular docking traditional medicine |
| title | Natural Anthraquinones as Potential Akt1-Targeted Anticancer Agents |
| title_full | Natural Anthraquinones as Potential Akt1-Targeted Anticancer Agents |
| title_fullStr | Natural Anthraquinones as Potential Akt1-Targeted Anticancer Agents |
| title_full_unstemmed | Natural Anthraquinones as Potential Akt1-Targeted Anticancer Agents |
| title_short | Natural Anthraquinones as Potential Akt1-Targeted Anticancer Agents |
| title_sort | natural anthraquinones as potential akt1 targeted anticancer agents |
| topic | akt1 anthraquinone cancer drug molecular docking traditional medicine |
| url | https://ajmb.umsha.ac.ir/PDF/ajmb-12-123.pdf |
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