Molecular docking, QSAR, pharmacophore modeling, and dynamics studies of some chromone derivatives for the discovery of anti-breast cancer agents against hormone-dependent breast cancer

Abstract

In search of new anti-breast cancer agents, the present study envisaged the design and synthesis of a series of benzopyran-chalcones. All the synthesized compounds were assayed for their in-vitro anticancer activity against ERþ MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines using SRB assay. The synthesized compounds were found active against ERþ MCF-7 cell lines. Based on the in-vitro data, in-sil ico analysis was performed using hormone-dependent breast cancer targets such as hER-a and aroma tase because the compounds showed activity against MCF-7 cells and none was active against MDA-MB 231. The in-silico results supported the in-vitro anticancer activity suggesting the affinity of compounds toward hormone-dependant breast cancer. Compounds 4A1 to 4A3 were found to be most cytotoxic to MCF-7 cells with IC50 values of 31.87, 22.95, and 20.34 lg/ml, respectively (Doxorubicin IC50: <10 lg/ml). In addition, they showed the interactions with the amino acid residues of a binding cavity of an hER-a. Furthermore, quantitative structure-activity relationship (QSAR) studies were performed to reveal the vital structural features required for anticancer activity against breast cancer. Molecular dynamic simulation studies of hER-a and 4A3 in comparison with the raloxifene complex ensure the appropriate refinement of compounds in the dynamic system. Additionally, a generated pharmacophore model explored the essential pharmacophoric features of the synthesized scaffolds with respect to clinically used drug mole cules for optimal hormone-dependant anti-breast cancer activity.