QSAR Study, Molecular Docking/Dynamics Simulations and ADME Prediction of 2-Phenyl-1H-Indole Derivatives as Potential Breast Cancer Inhibitors

Abstract

In the current investigation, QSAR studies have been performed on fifty-four analogs of the 2-phenyl-1H-indole analogs, which have antiproliferative activity against two cancer cells lines MDA MB231 and MCF-7.Partial least square (PLS) regression exhibited a good correlation between fitted and observed biological activities. The descriptive and predictive performances of QSAR models have been assessed and validated through internal and external validations. The leave-one-out cross-validation R2CV, the bootstrapping correlation coefficients R2boots and the predicted R2pred reveal a high predictive power for both models developed. Molecular docking/dynamics simulations results show that the ligands L39, L40, and L48 fit well in the pocket of the estrogen-α (PDB:1A52) and ligand L47 with the progesterone (PDB:1A28) confirmed by the high negative score values and by the several interactions ( H-bonds and hydrophobic interactions) which established between these ligands and the active site residues of both receptors. Finally, Drug-likeness and ADME prediction have revealed that the ligands L39, L40, and L48 complied with Lipinsky, Veber, and Egan rules that presented a good absorption and oral bioavailability, except the ligand L47. Clearly, this finding shows that these ligands could be used as potential precursors to developing breast cancer drugs.