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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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hamadan University of Medical Sciences
2024-12-01
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| Series: | Avicenna Journal of Medical Biochemistry |
| Subjects: | |
| Online Access: | https://ajmb.umsha.ac.ir/PDF/ajmb-12-123.pdf |
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| Summary: | 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. |
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| ISSN: | 2345-4113 |