Journal
CHEMMEDCHEM
Volume 16, Issue 23, Pages 3496-3512Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.202100473
Keywords
Mutual prodrugs; 5-Fluorouracil; 5-FU hybrids; 5-FU conjugates; Anticancer agents
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Funding
- PON R&I funds2014-2020 [CUP: E66C18001320007, AIM1872330]
- Universita degli Studi di Catania within the CRUICARE Agreement
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This review discusses the progress made in the development of 5-FU-based mutual prodrugs over the past decade to improve therapeutic efficacy and achieve targeted delivery to cancer tissues, aiming to minimize toxicity to healthy cells and reduce side effects.
The development of potent antitumor agents with a low toxicological profile against healthy cells is still one of the greatest challenges facing medicinal chemistry. In this context, the mutual prodrug approach has emerged as a potential tool to overcome undesirable physicochemical features and mitigate the side effects of approved drugs. Among broad-spectrum chemotherapeutics available for clinical use today, 5-fluorouracil (5-FU) is one of the most representative, also included in the World Health Organization model list of essential medicines. Unfortunately, severe side effects and drug resistance phenomena are still the primary limits and drawbacks in its clinical use. This review describes the progress made over the last ten years in developing 5-FU-based mutual prodrugs to improve the therapeutic profile and achieve targeted delivery to cancer tissues.
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