Hamadan University of Medical Sciences Avicenna Journal of Medical Biochemistry 2345-4113 12 2 2024 12 31 Natural Anthraquinones as Potential Akt1-Targeted Anticancer Agents 123 130 10.34172/ajmb.2567 EN Shokoofeh Jamshidi https://orcid.org/0000-0002-0646-1882 Fatemeh Mahfouzi https://orcid.org/0009-0005-7939-6048 Setareh Shojaei https://orcid.org/0000-0001-8323-1231 Amir Taherkhani https://orcid.org/0000-0002-6546-8785 Journal Article 10.34172/ajmb.2567 2024 11 06 2024 12 28 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.