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 ER + MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines using SRB assay. The synthesized compounds were found active against ER + MCF-7 cell lines. Based on the in-vitro data, in-silico analysis was performed using hormone-dependent breast cancer targets such as hER-α and aromatase 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 μg/ml, respectively (Doxorubicin IC₅₀: <10 μg/ml). In addition, they showed the interactions with the amino acid residues of a binding cavity of an hER-α. 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-α 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 molecules for optimal hormone-dependant anti-breast cancer activity.

Communicated by Ramaswamy H. Sarma

Communicated by Ramaswamy H. Sarma

Keywords:

• Chromone
• chalcones
• hormone-dependent breast cancer
• QSAR
• pharmacophore modelling
• dynamics simulations

Acknowledgments

The authors are thankful to Dr. H. N. More, Principal, Bharati Vidyapeeth College of Pharmacy for providing the necessary laboratory facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.