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 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.