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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   
Yazarlar (4)
Zuhal Alim
Kirsehir Ahi Evran University, Türkiye
Prof. Dr. Serap YALÇIN AZARKAN Prof. Dr. Serap YALÇIN AZARKAN
Kırşehir Ahi Evran Üniversitesi, Türkiye
Namik Kilinc
Bartin University, Türkiye
Ebru Akkemik
Siirt University, Türkiye
Devamını Göster
Özet
Hyperuricemia 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 mu M, 1.357 mu M, 1.788 mu M, 1.228 mu M 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 mu M) 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.
Anahtar Kelimeler
Xanthine oxidase | Inhibition | Breast cancer | Cytotoxicity | Molecular docking
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale
Dergi Adı Journal of Molecular Structure
Dergi ISSN 0022-2860 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q2
Makale Dili Türkçe
Basım Tarihi 09-2025
Cilt No 1340
DOI Numarası 10.1016/j.molstruc.2025.142497
Makale Linki https://doi.org/10.1016/j.molstruc.2025.142497