Synthesis and Medicinal Applications of N-Heterocyclic Carbene Complexes based on Caffeine and other Xanthines

ChemMedChem. 2024 Apr 26:e202400118. doi: 10.1002/cmdc.202400118. Online ahead of print.

Abstract

Xanthines are purine derivatives predominantly found in plants. These include compounds such as caffeine, theophylline, and theobromine and exhibit a variety of pharmacological properties, demonstrating efficacy in treating neurodegenerative disorders, respiratory dysfunctions, and also in cancer. The versatile attributes of these materials render them privileged scaffolds for the development of compounds for various biological applications. Xanthines are N-heterocyclic carbene precursors that combine a pyrimidine and an imidazole ring. Owing to their biological relevance, xanthines have been employed as N-heterocyclic carbenes in the development of metallodrugs for anticancer and antimicrobial purposes. In this conceptual review, we examine key examples of N-heterocyclic carbene complexes derived from caffeine and other xanthines, elucidating their synthetic methods and describing their pertinent medicinal applications.

Keywords: Medicinal Chemistry; Metal complexes; N-heterocyclic carbenes; caffeine; xanthines.