3D-QSAR and Docking Simulation Studies of Some Benzopyrone Derivatives as Inhibitors for Breast Cancer Stem Cell Growth via P-Glycoprotein Mediated Efflux

摘要

Benzopyrone derivatives (Coumarins) are well known inhibitors of P-glycoprotein (P-gp) mediated efflux. The high expression level of these efflux proteins promotes the growth of breast cancer stem cells (CSCs). The activity of breast CSCs is directly affected by the inhibition of efflux proteins by benzopyrone derivatives. Ligand based pharmacophoric study and structure based docking studies have been exploited for assessing this inhibitory activity. Based on QSAR results, a three point pharmacophore comprising of one hydrogen bond acceptor (A) and two condensed aromatic groups (R) has been designed. The atom based QSAR study was conducted to predict partial least square (PLS) statistical factors for test and training data sets. Some specific amino acids have been demonstrated to be actively involved in the ligand protein interaction. These structural features of ligands and active site residues of target protein provide new pathways to develop therapeutically important drugs for the inhibition of breast cancer stem cells.