English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Epidermal growth factor receptors are constitutively overexpressed in breast cancer cells, which in turn stimulate many downstream signaling pathways that are involved in many carcinogenic processes. This makes EGFR a striking target for cancer therapy. This study focuses on the EGFR kinase domain inactivation by novel synthesized indoline derivatives. The compounds used are N-(2-hydroxy-5-nitrophenyl (4’-methyl phenyl) methyl) indoline (HNPMI), alkylaminophenols − 2-((3,4-Dihydroquinolin-1(2H)-yl) (p-tolyl) methyl) phenol (THTMP) and 2-((1, 2, 3, 4-Tetrahydroquinolin-1-yl) (4 methoxyphenyl) methyl) phenol (THMPP). To get a clear insight into the molecular interaction of EGFR and the three compounds, we have used ADME/Tox prediction, Flexible docking analysis followed by MM/GB-SA, QM/MM analysis, E-pharmacophore mapping of the ligands and Molecular dynamic simulation of protein-ligand complexes. All three compounds showed good ADME/Tox properties obeying the rules of drug-likeliness and showed high human oral absorption. Molecular docking was performed with the compounds and EGFR using Glide Flexible docking mode. This showed that the HNPMI was best among the three compounds and had interactions with key residue Lys 721. The protein-ligand complexes were stable when simulated for 100 ns using Desmond software. The interactions were further substantiated using QM/MM analysis and MM-GB/SA analysis in which HNPMI was scored as the best molecule. All the analyses were carried out with a reference molecule—Gefitinib which is a known standard inhibitor of EGFR. Thus, the study elucidates the potential role of the indoline derivatives as an anti-cancer agent against breast cancer by effectively inhibiting EGFR. Communicated by Ramaswamy H. Sarma

Molecular interaction study of novel indoline derivatives with EGFR-kinase domain using multiple computational analysis