The Study of flavonoid in Apium graveolens L. as a Kirsten Rat Sarcoma Protein Inhibitor in Colorectal Cancer based on in silico Study

Abstract

Colorectal cancer (CRC) is the second deadliest cancer that is mostly caused by the mutation of Kirsten Rat Sarcoma (KRAS) type G12D, it’s still undruggable. Flavonoids are natural products found as the most important secondary metabolite in celery, consisting of apigenin, kaempferol, quercetin, and luteolin. This study aims to analyze the most potential flavonoid compounds in Apium graveolens L. as KRAS inhibitors in CRC with in-silico. This study starts by collecting the 3D structure, Compound ID, formula, and canonical SMILES of compounds from the PubChem, and collecting the 3D structure of KRAS G12D from the RCSB-PDB. Ligand and protein preparations using OpenBabel PyRx, and Biovia Discovery Studio 2019. Drug-likeness analyzed by SwissADME web server, biological activity by PassOnline web server, docking by PyRx VinaWizard, and visualization by Biovia Discovery Studio 2019. RMSF values were obtained by analyzing binding stability with CABS-flex web server. Chrysoeriol has the potential as an inhibitor of KRAS protein drug in CRC since the lowest toxicity and the smallest binding affinity bind the most strongly to the KRAS