Molecular Docking Study of Natural Compounds from Indonesian Medicinal plants as AKT and KRAS G12D Inhibitors Candidates

Resistance to anti-EGFR treatment in colorectal cancer may arise due to the loss of PTEN function or the presence of KRAS G12D mutation. These genetic events can lead to persistent activation of the PI3K-AKT or RAS-MAPK signaling pathways, respectively. Overcoming anti-EGFR resistance can be achieved by inhibiting these signaling pathways using AKT or KRAS G12D inhibitors. The exploration of plant-derived compounds with anticancer activity offers a promising avenue for discovering potential AKT or KRAS G12D inhibitors. Therefore, this study aimed to identify natural compounds from Indonesian medicinal plants that could be developed as AKT or KRAS G12D inhibitors using a molecular docking approach. The in-silico screening of natural compounds involved the utilization of oral drug parameters. Subsequently, the filtered natural compounds were docked into the binding sites of respective proteins. The analysis involved evaluating the AutoDock Vina scoring function and examining the ligand interactions with residues within the binding site to assess the potential of the natural compounds. The findings revealed that among the 1311 natural compounds from 320 Indonesian medicinal plant species, 274 compounds met the oral drug parameters and predicted to pose anticancer activities based on QSAR analysis. Notably, morindone and porphyrin demonstrated the highest potential for development as AKT inhibitors, while phaseollin exhibited the most potential as a KRAS G12D inhibitor.