Molecular docking of novel 5-O-benzoylpinostrobin derivatives as wild type and L858R/T790M/V948R mutant EGFR inhibitor.

Abstract

Background Previous studies have shown that 5-O-benzoylpinostrobin derivatives is a potential anti-breast cancer, with the highest potential being the HER2 inhibitors, is a protein's member of the epidermal growth factor receptor (EGFR) family. Overexpression of EGFR itself is known to be one of the causes of other cancer, including non-small cell lung cancer (NSCLC). Thus, it is possible that 5-O-benzoylpinostrobin derivatives can also inhibit the overexpression of EGFR in NSCLC. In the case of NSCLC, mutations of EGFR are often found in several amino acids, such as L858R, T790M, and V948R. This study aimed to determine the potential of 5-O-benzoylpinostrobin derivatives as an inhibitor of wild type and L858R/T790M/V948R-mutant EGFR. Methods Docking was performed using AutoDock Vina 1.1.2 on both wild type and L858R/T790M/V948R-mutant EGFR. Parameters observed, consisted of free energy of binding (ΔG) and amino acid interactions of each ligand. Results Docking results showed that all 5-O-benzoylpinostrobin derivatives showed a lower ΔG for both wild type and L858R/T790M/V948R-mutant EGFR, with the lowest ΔG shown by 4-methyl-5-O-benzoylpinostrobin and 4-trifluoromethyl-5-O-benzoylpinostrobin. Both the ligands have the similarity of interacting amino acids compared to reference ligands between 76.47 and 88.24%. Specifically, the ΔG of all test ligands was lower in mutant EGFR than in the wild type, which indicates the potential of the ligand as EGFR inhibitors where a mutation to EGFR occurs. Conclusions These results confirm that 5-O-benzoylpinostrobin derivatives have the potential to inhibit EGFR in both wild type and L858R/T790M/V948R-mutant.