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Anti-Cancer Drugs

Anti-Cancer Drugs

IF: 1.8
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Differential functionality of fluoropyrimidine nucleosides for safe cancer therapy.

Published:1 November 2024 DOI: 10.1097/CAD.0000000000001644 PMID: 39012759
Tim Holzinger,?Julia Frei,?Natalia Teresa Jarzebska,?Hans-Dietmar Beer,?Thomas M Kündig,?Steve Pascolo,?Severin L?uchli,?Mark Mellett

Abstract

Chemotherapies are standard care for most cancer types. Pyrimidine analogs including 5-fluorouracil, cytosine arabinoside, 5-azacytidine, and gemcitabine are effective drugs that are utilized as part of a number of anticancer regimens. However, their lack of cell-specificity results in severe side effects. Therefore, there is a capacity to improve the efficacy of such therapies, while decreasing unwanted side effects. Here, we report that while 5-fluorocytosine is not chemotherapeutic in itself, incorporated into a ribonucleoside and more importantly into an RNA oligonucleotide, it induces cytotoxic effects on cancer cells in vitro . Interestingly, these effects are rescued by both uridine and thymidine. Similarly, in-vitro 2'-deoxy-5-fluorocytidine inhibits the growth of tumor cells but has the advantage of being less toxic to human primary cells compared with 5-fluorocytidine, suggesting that the deoxyribonucleoside could exhibit less side-effects in vivo . Thus, this work indicates that the potency of 5-fluorocytidine and 2'-deoxy-5-fluorocytidine should be further explored. In particular, oligonucleotides incorporating 5-fluorocytosine could be novel chemotherapeutic drugs that could be formulated in cancer-specific particles for safe and efficacious cancer treatments.

Substances (8)

Related products
Procduct Name CAS Molecular Formula Supplier Price
5-Fluorouracil 51-21-8 C4H3FN2O2 1108 suppliers $5.00-$3543.55
5-Fluorocytosine 2022-85-7 C4H4FN3O 949 suppliers $3.00-$1500.00
Uridine 58-96-8 C9H12N2O6 936 suppliers $5.00-$37700.00
Thymidine 50-89-5 C10H14N2O5 848 suppliers $5.00-$2348.86
5-Azacytidine 320-67-2 C8H12N4O5 813 suppliers $7.00-$1952.50
Cytarabine 147-94-4 C9H13N3O5 808 suppliers $5.00-$3650.00
Gemcitabine 95058-81-4 C9H11F2N3O4 677 suppliers $5.00-$6080.00
2'-DEOXY-5-FLUOROCYTIDINE 10356-76-0 C9H12FN3O4 168 suppliers $9.00-$2390.00

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