Targeting AKT1 in Oral Cancer: In Silico Insights from Chrysanthemum morifolium Phytoconstituents

Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer known to be closely associated with the activation of the PI3K/AKT/mTOR pathway, particularly the AKT1 protein, which plays a critical role in cancer cell proliferation, migration, and survival. This study aims to evaluate the potential of bioactive compounds from Chrysanthemum flowers (Chrysanthemum morifolium) as AKT1 inhibitor candidates using an in silico approach. A total of 30 bioactive compounds were then analyzed through drug-likeness assessment based on Lipinski’s rule, ADME-Tox prediction, pharmacophore screening, and molecular docking against the AKT1 receptor (PDB ID: 3CQW). The results revealed that 17 out of 30 compounds complied with Lipinski’s rule, while all compounds were successfully identified as hits in the best pharmacophore model with an AUC value of 0.70. Molecular docking for the compounds then were validated using the protein’s original ligand, yielding a reliable RMSD value of 0.76 Å. Apigenin-7-O-glucuronide exhibited the highest pharmacophore fit score of 34.42, whereas apigenin-7-O-glucoside demonstrated the best binding affinity with a binding energy of -10.29 kcal/mol, which was lower than the reference compound Capivasertib (-9.52 kcal/mol). However, based on the integration of all evaluated parameters, apigenin exhibited the most balanced profile, characterized by compliance with Lipinski’s rule, favorable ADME-Tox properties, a pharmacophore fit score of 34.22, and the lowest inhibition constant value of 0.00193 µM. Collectively, apigenin holds strong potential as a promising AKT1 inhibitor candidate for the development of OSCC therapeutics and warrants further investigation through in vitro and in vivo studies.