Comprehensive Assessment of 2-(3-Methoxyphenylamino)-2-Oxoethyl Methacrylate: Spectroscopic, Computational, Toxicological, Molecular Docking and Dynamic Studies with STAT3 Protein

Abstract

In this study, we successfully resynthesized the compound 2-(3-methoxyphenylamino)-2-oxoethyl methacrylate (3MPAEMA) and characterized it using experimental spectroscopic methods and advanced computational analyses. Theoretical investigations encompassed Natural Bond Orbital (NBO) analysis, Band Gap (BG) calculations, Molecular Electrostatic Potential (MEP) mapping, and Density of States (DOS) evaluations, offering a comprehensive understanding of the molecule's electronic structure. We also employed thermochemical parameters, electronic descriptors, and Non-Covalent Interaction (NCI) analyses to assess the compound’s stability, reactivity, and intramolecular interactions. We performed toxicological profiling through in silico oral toxicity prediction models, validating model performance metrics. We conducted molecular docking and 50-ns molecular dynamics (MD) simulations to elucidate the binding behavior of 3MPAEMA with the oncogenic transcription factor STAT3, specifically targeting its SH2 domain. Docking studies revealed a strong binding affinity, while MD simulations confirmed the structural stability of the 3MPAEMA–STAT3 complex. Collectively, these results underscore the promising potential of 3MPAEMA as a STAT3-targeting agent in anticancer therapy. However, further in vitro and in vivo investigations must confirm its therapeutic potential. This comprehensive study offers valuable insights into the physicochemical, toxicological, and biological attributes of 3MPAEMA, supporting its candidacy for future biomedical applications.