Understanding the Anti-Cancer Potentialof Linalool on Colorectal Cancer Through an In Silico Approach

Introduction: Colorectal cancer (CRC) is the fourth most commoncause of cancer-related mortality. One subtype of CRC isBRAF mutations, which is a proto-oncogene involved in cellproliferation through the MAPK signaling pathway. This groupis characterized by a median survival of fewer than ۱۲ months.Therefore BRAF is an important therapeutic target in coloncancer. Chemotherapy is an effective treatment for CRC, butit has serious side effects and the current anticancer drugs areexpensive. So, there is an urgent need to find effective, inexpensiveanticancer compounds with fewer side effects.The aim of this study was to examine the anticancer effectsof linalool, which is a linear monoterpene, and its derivativesagainst colorectal cancer target protein (BRAF).Methods: This is a descriptive-analytic research project. Regorafenib(DrugBank Accession Number: DB۰۸۸۹۶), a BRAFinhibitor drug, was considered as a positive control.BRAF protein structure was obtained from Protein Data Bank(PDB), and PubChem was used to collect linalool and its derivativeschemical structure.Molecular docking was performed using MVD (molegro virtualdocker), version ۶, with a grid resolution of ۰.۳۰ A. Thecalculated ligand receptor interaction energy is represented bydocking scores (DOS). Thus, more negative scores represent astronger binding affinity.Results: The docking of BRAF protein investigated with linalooland its derivatives, revealed that Linalool ۳,۶-oxideprimeveroside (PubChem ID ۱۳۲۲۸۲۰۶۰) had the best DOS(-۱۳۸.۳۲۸), which was the closet score to Regorafenib DOS(-۱۵۹.۶۴۵).Conclusion: The results revealed that Linalool ۳,۶-oxide primeverosideis a potent inhibitor of BRAF. On the basis of thefindings. It is recommended that in-vitro and in-vivo studies becarried out to determine the efficacy of this natural compoundagainst colorectal cancer.