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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290623PMC
http://dx.doi.org/10.1002/cmdc.202100473DOI Listing

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Article Synopsis
  • Colon cancer is a significant health issue in industrialized countries, with 5-Fluorouracil (5-FU) often causing side effects and resistance in treatment.
  • Recent research has explored using HO-1 inhibitors in combination with 5-FU, showing potential effectiveness against cancer cells.
  • The study found that specific drug hybrids (SI1/22) outperform 5-FU in colon cancer by enhancing ROS levels and promoting cell death through apoptosis and autophagy.
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