QSAR of Acyl pinostrobin derivatives as Anti-breast cancer against HER-2 receptor and their ADMET properties based on in silico Study

Abstract

Pinostrobin is a compound with potential anti-breast cancer activity, but its activity is lower than the drugs used clinically. Modifying pinostrobin to form 9 acyl pinostrobin derivatives (AP1-AP9) is a method that changes physicochemical properties to affect the activity and ADMET properties. This study aims to predict the anti-breast cancer activity of pinostrobin and acyl pinostrobin derivatives against HER-2 receptor by molecular docking, obtain the most influential descriptor by QSAR study, and predict ADMET properties of these compounds. The molecular docking was using MVD on the HER-2 receptor (5JEB.pdb). The parameters observed were the Rerank Score (RS) and the amino acid residues. The physicochemical properties (logP, total energy, and molecular weight) for the QSAR study were determined using Chem Draw and Chem 3D. The QSAR study was carried out using SPSS. Prediction of ADMET properties was determined using the pkCSM. The molecular docking result showed that all acyl pinostrobin derivatives have a lower RS than pinostrobin. The lowest RS was indicated by pinostrobin nonanoate (AP8) with a value = -108,156 kcal/mol. The influential parameters in the QSAR study were the logP and MW. The results of this study also showed that the ADME properties of acyl pinostrobin derivatives were mainly better than pinostrobin, and all derivatives were also less toxic than pinostrobin. These results indicate that acyl pinostrobin derivatives, especially pinostrobin nonanoate (AP8), can be further synthesized as anti-breast cancer by considering the QSAR study's best equation.