Multifaceted In Silico and DFT-Based Analysis of 2-Aminosuccinic Acid on Ferroptosis-Related Targets

Abstract Metabolic reprogramming and redox imbalances in cancer cells play a significant role in tumor growth and development of treatment resistance. In recent years, ferroptosis, a type of programmed cell death characterized by iron-dependent lipid peroxidation, has emerged as a promising target for cancer therapy. Amino acid transport, glutathione (GSH) homeostasis, and antioxidant defense mechanisms are critically important in the regulation of ferroptosis. In this study, the interactions of 2-aminosuccinic acid, involved in amino acid metabolism, with key molecular targets associated with ferroptosis were investigated using an in silico molecular docking approach. Docking analyses revealed that the compound showed significant binding affinities with SLC1A1 (EAAT3), SLC7A11 (xCT), and the GPX4/GSH system. The observed binding energy of −5.0 kcal/mol with SLC7A11 is noteworthy in terms of modulating intracellular cysteine/glutathione balance and regulating ferroptosis sensitivity. These findings suggest that 2-aminosuccinic acid may be a potential molecule capable of influencing ferroptosis in cancer cells via amino acid transport and redox regulation. In addition, the structural, electronic, spectroscopic, and thermodynamic properties of 2-aminosuccinic acid were extensively investigated using density functional theory (DFT) with the 6-311G basis set. The molecule’s geometry was optimized to a stable conformation, and the calculated bond lengths followed values reported in the literature. The HOMO–LUMO energy gap (ΔE = 3.308 eV) indicated that the molecule has high kinetic stability and low chemical reactivity. Theoretical FT-IR, 1H NMR, and 13C NMR spectra confirmed the functional groups, while UV–vis analyses revealed strong absorptions in the 150–200 nm range due to π→π* and n→π* transitions. Molecular electrostatic potential (MEP) maps have shown that oxygen atoms form reactive centers as electron-rich regions. Non-covalent interaction (NCI) and Hirshfeld surface analyses revealed that crystal packing is largely stabilized by O···H and H···O hydrogen bonds. Thermo-chemistry map (TCM) analyses detailed the temperature-dependent behavior of thermodynamic parameters such as heat capacity and entropy in the 300–900 K temperature range. This study presents a holistic approach to both the interactions of 2-aminosuccinic acid with ferroptosis-related molecular targets and its fundamental theoretical properties; the findings suggest that this compound could be a potential candidate for future applications in cancer treatment, ferroptosis-targeted drug design, and medicinal chemistry.