In-silico and in-vitro identification of triazole based compounds as potential EGFR inhibitors targeting lung cancer

Abstract

ABSTRACTThe use of FDA-approved drugs for the therapy of lung cancer through drug repurposing is a noteworthy approach. We retrieved all the FDA-approved triazole-based drugs from Drugbank and conducted docking-based virtual screening of the triazole-based FDA-approved drugs against the EGFR target. Deferasirox demonstrated hydrogen bonding interactions with residues Thr 830, Asp 831, Lys 721 and Met 769 of the EGFR-TKD receptor (PDB ID: 1M17) and Posaconazole showed hydrogen bonding with residues Met 769 and Glu 734 of the similar EGFR receptor along with the binding energies of −9.60, −9.50, kcal/mol respectively. The dock score for reference molecule found to be −6.70 (kcal/mol). Best two ligands (Deferasirox and Posaconazole) were selected on the basis of dock score from the virtual screening results for in vitro NRU assay using A549 cells to determine their cytotoxicity and cell viability. During the in vitro NRU experiment, Deferasirox and Posaconazole demonstrated IC50 values of 114.9 and 910.2 µM, respectively. MD simulations were performed to investigate the dynamic behaviour and stability, and interactions were compared to the standard inhibitor for the EGFR target. DFT studies were carried out to determine their molecular properties, including their electronic structure, bond lengths and bond energies. The results of the in silico and in vitro studies were analysed to assess the potential of Deferasirox and Posaconazole for use as anticancer agents in the mitigation of lung cancer symptoms. This study focused on repurposing FDA-approved triazole-based compounds to identify their potential as effective lung cancer treatments with anticancer properties.KEYWORDS: Lung cancerin-silicoin-vitrodrug repurposingEGFR AcknowledgmentsThe authors express their gratitude to the Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh 173 229, India, for the support.Disclosure statementNo potential conflict of interest was reported by the author(s).