Abstract
Background: Epidermal growth factor receptor (EGFR, ErBb) belongs to family of receptor tyrosine kinase (RTKs) that plays an important role in multiple cell signaling pathways, which includes cell growth, multiplication apoptosis, etc. Overexpression of EGFR results in development of malignant cells. Therefore, EGFR is considered one of the important target for cancer therapy.
Objective: In this study, virtual screening of 329 flavonoids obtained from the Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target (NPACT) database had been performed to identify novel EGFR inhibitors.
Materials and Methods: Virtual screening of flavonoids were carried out using different in silico methods, which includes molecular docking studies, prediction of druglikeness, in silico toxicity studies and bioactivity prediction.
Results: Six flavonoids NPACT00061, NPACT00062, NPACT00066, NPACT00280, NPACT00700 and NPACT00856 were identified as potential EGFR inhibitors with good docking score and druglikeness properties. In the in silico toxicity studies, compound NPACT00061, NPACT00062, NPACT00066 and NPACT00856 were found to be carcinogenic. Finally, two flavonoids NPACT00280 and NPACT00700 were recognized as novel EGFR inhibitors.
Conclusion: Our findings suggest that compound NPACT00280 and NPACT00700 could be further explored as novel EGFR inhibitors.
Keywords: Virtual screening, flavonoids, NPACT database, EGFR inhibitors, receptor tyrosine kinase (RTKs), apoptosis.
Graphical Abstract
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