Synthesis and initial <i>in vitro</i> evaluation of olmutinib derivatives as prospective imaging probe for non-small cell lung cancer

Introduction: Imaging a non-small cell lung cancer (NSCLC) using radiolabeled tyrosine kinase inhibitors (TKIs) has attracted attention due to their unique interaction with the target epidermal growth factor receptor (EGFR). Olmutinib (OTB) is one of third-generation EGFR TKIs, which selectively inhibit L858R/T790M mutation. In this study, we aim estimate iodinated OTB (I-OTB)-receptor complex by molecular docking. Furthermore, will synthesize I-OTB and evaluate its activity toward in vitro cytotoxicity assay. Methods: A docking simulation was carried out an AutoDock Vina program package ligand-receptor complex. The I-OTB, N-{3-iodo-5-[(2-{[4-(4-methylpiperazin-1-yl)phenyl]aminothieno{3,2-d}pyrimidin-4-yl)oxy]phenyl} acrylamide, synthesized introducing iodine atom phenyl group 3-aryloxyanilide structure. half inhibitory concentration (IC50) determined employing 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt (WST-8) assay I-OTB. Results: study exhibited that could take similar parent compound. We successfully confirmed structure instrumental analysis. binding energy T790M are -8.7 -7.9 kcal/mol, respectively. showed also affinity towards mutation IC50 10.49 ± 5.64