Hamadan University of Medical Sciences Avicenna Journal of Dental Research 2423-7582 16 4 2024 12 30 Therapeutic Targeting of Akt1 in Oral Squamous Cell Carcinoma Using Natural Cinnamic Acids 210 217 10.34172/ajdr.1879 EN Setareh Shojaei https://orcid.org/0000-0001-8323-1231 Amirhoseyn Naiini https://orcid.org/0009-0009-2062-6039 Shokoofeh Jamshidi https://orcid.org/0000-0002-0646-1882 Amir Taherkhani https://orcid.org/0000-0002-6546-8785 Journal Article 10.34172/ajdr.1879 2024 05 31 2024 11 01 Background: Akt1, a serine/threonine kinase, plays a central role in cancer development and progression. Its overexpression correlates with aggressive phenotypes and poor prognosis in several types of cancers, such as oral squamous cell carcinoma (OSCC). Cinnamic acid derivatives (CADs) from natural sources exhibit anticancer properties, making them potential Akt1 inhibitors. Methods: The binding affinities of 19 CADs to the Akt1 catalytic cleft were evaluated using molecular docking simulations and then compared with the Akt1 inhibitor capivasertib. Interaction modes were analyzed to identify critical residues involved in ligand binding. Results: Cynarin demonstrated the highest binding affinity (ΔGbinding =-13.46 kcal/mol, Ki=136.48 pM), forming three hydrogen bonds with Akt1. Rosmarinic acid with six hydrogen bonds also exhibited potent inhibition (ΔGbinding =-11.51 kcal/mol , Ki=3.67 nM). Both compounds represented superior binding compared to capivasertib. Conclusion: Cynarin and rosmarinic acid from natural sources showed promising inhibitory potential against Akt1, suggesting their therapeutic values as anticancer agents targeting the PI3K/Akt pathway in OSCC.