Recent Expansions in the Potential of Uracil Derivatives as Chemotherapeutic, Antimicrobial, and Antiviral Agents: A Review

Uracil is a privileged scaffold in medicinal chemistry, playing a crucial role in the development of therapeutic agents. Clinically used uracil analogs, such as 5-fluorouracil, tegafur, carmofur, and floxuridine, have shown significant anticancer potential. However, their clinical applications are limited by poor selectivity, central nervous system toxicity, and gastrointestinal side effects. To overcome these challenges, structural modifications and hybridization with other pharmacophores have been explored, enhancing therapeutic efficacy and selectivity. This review highlights recent advancements (post-2013) in the chemistry and biological activity of uracil derivatives, categorizing them into 5-halo-uracils, substituted uracils, uracil nucleosides, uracil-based hybrids, organometallic derivatives, thiouracils, prodrugs, and fused uracils. Their anticancer activity is primarily linked to DNA biosynthesis inhibition and cell cycle arrest, while their antiviral and antimicrobial effects arise from disrupting key steps in viral replication and bacterial growth. Promising results have been observed against HIV, HCMV, herpes viruses, Staphylococcus aureus, Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa, Trypanosoma, and Leishmania species. This review aims to inspire medicinal chemists to develop highly selective, less toxic, and more potent uracil-based chemotherapeutic, antiviral, and antimicrobial agents for future clinical applications.