Design, Synthesis, and Molecular Docking Studies of Triazolylpyridine and Triazolylpyridinylbenzofuran Hybrids as Potential EGFR Inhibitors

A series of multi-pendant pharmacophoric organic compounds, including triazolylpyridine and triazolylpyridinylbenzofuran hybrids, were synthesized via a one-pot, eco-friendly approach using In(OTf)₃ as a catalyst. The reaction utilized phenacyl triazoles, 3-formyl chromones, and ammonium acetate as key precursors. The synthesized compounds were further investigated for their potential as lung cancer therapeutics through molecular docking studies targeting the EGFR receptor. Notably, these hybrids exhibited higher binding affinities than Gefitinib, a first-line lung cancer drug. These promising results suggest that these novel compounds could be viable candidates for potential EGFR inhibitors in future anti-cancer drug development.

Abstract

This study presents an innovative one-pot multicomponent synthesis of novel triazolyl-pyridine derivatives using phenacyl triazole, 3-formylchromones, and ammonium acetate under In(OTf)₃ catalysis. These derivatives were further elaborated into triazolylpyridinylbenzofuran hybrids, combining multiple pharmacophores into a single scaffold. The method offers a green, efficient, and high-yielding synthetic route. In silico studies assessed their therapeutic potential as epidermal growth factor receptor (EGFR) inhibitors. Remarkably, molecular docking revealed stronger binding affinity than Gefitinib, a standard lung cancer drug. These results position the synthesized hybrids as promising candidates for targeted anticancer therapy, meriting further biological investigation.

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