Ligand-based virtual screening, molecular docking, QSAR and pharmacophore analysis of quercetin-associated potential novel analogs against epidermal growth factor receptor

Abstract

The present study was to explore expectation and examination of therapeutic potential quercetin analogs as efficient anticancer agents against human epidermal growth factor receptor (EGFR), which is a consistent hallmark for moderating the non-small-cell lung carcinoma (NSCLC). Here, ligand-based virtual screening, pharmacophore approach and molecular docking were established as rational strategies for recognition of small analogs against the ligand binding domain of EGFR (PDB code: 1XKK). Adverse effects, toxicogenomics and pharmacokinetics reported that 10 candidates showed reliable consequences with less side effects and more efficient for target receptor. Protein–ligand interaction profiles revealed that the probable H-bonds, atomic-π contacts, salt bridges and van der Waals interactions sustain the complexity and stability of receptor structure; thus, they could complicate to generate single alteration acquired for drug resistance. In silico anticancer properties explain the lead scaffolds which are assumed to be flexible and experimentally proved chemicals. The overall consequences indicated that recognized leads could be utilized as reference skeletons for new inhibitors envisaging toward EGFR to ameliorate NSCLC and other malignant disorders.

Keywords:

• EGFR
• quercetin
• ligand-based virtual screening
• molecular docking
• QSAR-based clustering
• ADME/Tox analysis

Acknowledgements

We are very grateful to the Journal Editor, anonymous reviewers and Prof. P. Sreedhara Reddy, Department of Physics, Sri Venkateswara University, Tirupati, for their useful comments, which greatly helped to improve the scientific content of the original paper.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

B. Uma Devi is thankful to the University Grants Commission (UGC), New Delhi, India, for providing financial help for the research work through Rajiv Gandhi National Fellowship (RGNF) (F1–17.1/2012–13/RGNF-2012–13-SC-AND-32761/(SA-III/WEBSITE)) and Y. Suneetha is thankful for Human Resource Development for Health Research, New Delhi (F. No. V0.25011/542-HRD/2016-HR) to carry out this work.