Design and Molecular Docking of Novel 5-O-Benzoylpinostrobin Derivatives as Anti-Breast Cancer

Abstract

This study aims to design the 5-O-Benzoylpinostrobin derivative with the most potent anti-breast cancer activity along with the most dominant type of receptor for the compound. Molecular docking was performed using AutoDock 4.2.6 on four types of breast cancer receptors consisting of ERα and β, PR, and HER2, both in the form of binding to agonist and antagonist ligands. The parameters used were the free energy of binding (ΔG) and the dissociation constant (Ki) as an affinity marker and similarity of amino acid residues as interactions similarity indicator. The benzoylpinostrobin derivative shows affinities for all receptors, but the highest was shown against HER2 receptors by 4-Nitro-5-O-benzoylpinostrobin. The ligand provided the most negative ΔG and the lowest Ki toward the antagonist form of HER2 with -12.79 kcal/mol and 0.42 nM, respectively. That affinity is four times higher than lapatinib which is known as potent HER2 inhibitor. Interestingly, the ligand has fewer van der Waals interactions with amino acids than lapatinib but the affinity shown is higher. Based on the study result, it can be considered that 4-Nitro-5-O-benzoylpinostrobin was the most potential modifications of pinostrobin as anti-breast cancer, especially for HER2-positive breast cancer.