Unveiling the Potential of Morpholinium Surface Active Ionic Liquids for Epidermal Growth Factor Receptor Inhibition: Synthesis, Integrating Molecular Docking, Dynamics, and In Vitro Studies

Abstract

Aim: To explore the potential for epidermal growth factor receptor (EGFR) inhibition by synthesizing two morpholinium-containing surface active ionic liquids (SAILs) with long alkyl side chains: N-dodecyl-N-methylmorpholinium salicylate ([C12mmor] [Sal]) and N-dodecyl-N-methylmorpholinium 3-hydroxy-2-naphthoate ([C12mmor][3-H-2-n]). Methods: Synthesis of SAILs by quaternization and neutralization metathesis reactions, molecular docking, simulation, and in vitro studies were integrated. Specifically, this finding draws attention to the pressing global issue of cancer-related mortality and underscores the pivotal role of inhibiting the EGFR in addressing nonsmall cell lung cancer, which is a leading cause of cancer deaths worldwide. Results: The data indicating lower inhibitory concentration values for A549 cells than for healthy cells underscore the promising potential of SAILs as potential active agents in cancer therapy. Their ability to exhibit cytotoxic effects specifically on cancer cells while sparing healthy cells has significant implications for targeted cancer treatment strategies. This selectivity not only minimizes the risk of adverse effects on healthy tissues but also enhances the therapeutic efficacy of ILs in combating cancer progression. Conclusion: These findings pave the way for further exploration of SAILs as potential candidates for therapeutic applications, particularly in lung cancer therapy using animal models of malignancies. However, clinical applications in terms of regulatory approval, biocompatibility, and synergistic action with drugs to ensure patient safety are necessary.