Zuhal AlımSerap Yalçın AzarkanNamık KılınçEbru Akkemik2025-05-132025-05-132025-09Alım, Z., Azarkan, S. Y., Kılınç, N., & Akkemik, E. (2025). Rating of In Vitro Cytotoxicity Activities and Anti-Xanthine Oxidase Activities of Some Non-Proteoneogenic Amino Acid Derivatives by Molecular Docking and Molecular Dynamics Studies. Journal of Molecular Structure, 142497.0022-2860https://doi.org/10.1016/j.molstruc.2025.142497https://hdl.handle.net/20.500.12604/8662Hyperuricemia is a chronic disease closely associated with many pathological conditions, including cancer, which occur due to increased uric acid levels. Xanthine Oxidase (XO) facilitates the stepwise conversion of hypoxanthine to xanthine and subsequently to uric acid, serving a crucial function in purine metabolism. XO inhibitors are the most important therapeutic agents for the control of hyperuricemia. The fact that existing XO inhibitors have serious side effects has made it necessary to describe original, impressive inhibitors with minor side effects. In this study, since the close relationship between hyperuricemia and cancer, the inhibition effects of some non-proteogenic amino acid derivatives (1-4) on XO activity and their cytotoxic effects on triple-negative breast cancer cell line (MDA-MB-231) were examined together. The inhibition effects of molecules 1-4 on XO activity were determined by IC50 values, and for XO, IC50 values of 1-4 were found to be 1.338 µM, 1.357 µM, 1.788 µM, 1.228 µM respectively. The cytotoxic effect of the molecules (1-4) on MDA-MB-231 cell lines was investigated by XTT analysis. According to the results obtained, it is seen that the effect of the 2nd (IC50:98.55 µM) molecule is more toxic on the cells than the others and molecule 2 demonstrated significant inhibition of cell migration in MDA-MB-231 cells in a compared to the untreated control. The study was supported by molecular docking and molecular dynamics and ADME analyses. In conclusion, the results of this study may be useful in the design of XO inhibitor drugs for the treatment of hyperuricemia by contributing to the synthesis of new, effective amino acid-derived XO inhibitors with fewer side effects.info:eu-repo/semantics/closedAccessBreast cancerCytotoxicityInhibitionMolecular dockingXanthine oxidasejournal-article13402-s2.0-10500402583510.1016/j.molstruc.2025.142497