| Title |
Bacterial cytidine deaminases as versatile activators of fluoropyrimidine nucleoside prodrugs |
| Authors |
Preitakaitė, Viktorija ; Kazlauskas, Arūnas ; Aučynaitė, Agota ; Butkutė, Kamilė ; Lapinskaitė, Ringailė ; Urbelienė, Nina ; Laurynėnas, Audrius ; Meškys, Rolandas |
| DOI |
10.1016/j.ejmech.2025.117860 |
| Full Text |
|
| Is Part of |
European journal of medicinal chemistry.. Elsevier BV. 2025, vol. 296, art. no. 117860, p. 1-16.. ISSN 0223-5234. eISSN 1768-3254 |
| Keywords [eng] |
cytidine deaminases ; 5-Fluoropyrimidine nucleosides ; enzyme-prodrug therapy |
| Abstract [eng] |
A platform for modification of 5-fluoropyrimidine nucleosides as potential prodrugs has been developed utilizing bacterial-derived cytidine deaminases (CDAs) for activation. It has been demonstrated that CDA_EH, CDA_F14, and CDA_Lsp effectively convert 5-fluoropyrimidine analogs into 5-fluoro-(2′-deoxy)uridine exhibiting cytotoxic effects. Prodrug activation, leading to reduced viability in CDA-expressing cells, has been observed in HCT116, MCF7, and U87MG cancer cell lines. This framework allows the evaluation of various N 4-acyl/alkyl-5-fluorocytidines, 4-alkylthio-5-fluorouridines, 4-alkoxy-5-fluoro- and 4-alkoxy-5-fluoro-2′-deoxyuridines for their potential use in enzyme-prodrug therapy. Overall, the developed platform provides valuable guidance on selecting both enzyme and prodrug components for the development of effective enzyme-prodrug strategies. |
| Published |
Elsevier BV |
| Type |
Journal article |
| Language |
English |
| Publication date |
2025 |
| CC license |
|
