Mutual Prodrugs of 5‐Fluorouracil: From a Classic Chemotherapeutic Agent to Novel Potential Anticancer Drugs
Valeria Ciaffaglione, Maria Modica, Valeria Pittalà, Giuseppe Romeo, Loredana Salerno, Sebastiano Intagliata
Abstract
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.