In Silico Identification of Novel Flavonoids Targeting Epidermal Growth Factor Receptor

Abstract

Background: Epidermal growth factor receptor (EGFR, ErBb) belongs to family of receptor tyrosine kinase (RTKs) played important role in multiple cell signaling pathways, which includes cell growth, multiplication and apoptosis etc. Overexpression of EGFR results in to development of malignant cells. Therefore EGFR considered as one of the important target for cancer therapy. Objective: In this study we performed virtual screening of 329 flavonoids obtained from Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target (NPACT) database to identify novel EGFR inhibitors. Materials and methods: Virtual screening carried out using different insilico methods which includes molecular docking studies, prediction of druglikeness, insilico 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 insilico 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.

Antiviral and Immunomodulatory Effects of Pelargonium sidoides DC. Root Extract EPs® 7630 in SARS-CoV-2-Infected Human Lung Cells

“…Whereas measles and mumps virus mainly use CD150 and CD46 (measles virus) (Hashimoto et al, 2002), or sialic acids and glycan motifs (mumps virus) (Kubota et al, 2016;Kruger et al, 2018;Kubota et al, 2019) for entry, RSV was shown to use distinct cell surface molecules, including glycosaminoglycans (GAG), intercellular adhesion molecule 1 (ICAM-1), and epidermal growth factor receptor (EGFR) (Battles and McLellan, 2019). Previous studies suggested that flavonoids inhibit GAG synthesis (Moskot et al, 2015;Qiu et al, 2017), block ICAM-1 induction (Chen et al, 2004;Owens et al, 2009), and inhibit EGFR (Firdous et al, 2014;Shah and Seth, 2021), potentially explaining the differential antiviral activity of EPs 7630 against RSV and the two paramyxoviruses measles and mumps virus. In line with these reports, it appears conceivable that EPs 7630 targets additional, yet unidentified host cell surface molecules involved in virus attachment, thereby also potentially limiting TMPRSS2-independent entry.…”

Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach

“…In addition, during the re-docking, the RMSD values of the selected compounds were ≤ 2.0 Å in the present study, which agree with the findings of Ramirez and Caballero [ 33 ], wherein ≤ 2.0 Å of RMSD corresponds to the good docking solutions. In the virtual screening of 329 naturally occurring plant-based flavonoids, six flavonoids were found to be potential EGFR inhibitors with good docking scores [ 34 ]. Sepay et al [ 35 ] have reported that Rhamnocitrin derivative Tupichinols E from Tupistra chinensis showed 1.4 times more binding affinity with EGFR tyrosine kinasethan Osimertinib (a well-known EGFR inhibitor).…”

Elucidation of the inhibitory potential of flavonoids against PKP1 protein in non-small cell lung cancer

“…A total of forty-six phytocompounds and one standard drug have been selected from the NPACT (20) and Pub-Chem databases. Only those flavonoids were selected for this study which have not been studied earlier for the treatment of lung cancer were.…”