Recent Advances in Metal Binding Pharmacophores Targeting Metalloenzymes

Metalloenzymes are widely distributed in a variety of organisms, and closely related with human diseases, which hence are considered as a wide range of important drug targets. Although several inhibitors targeting metalloenzymes have been approved for clinical use, there are a lack of drug candidates or high-quality inhibitors for most metalloenzymes, of which even many have not been exploited. Discovery of novel drugs targeting metalloenzymes is still one of important fields. Due to the distinctiveness of metal ions-containing active sites of metalloenzymes, the metalloenzyme inhibitors often bear a specific chemical moiety that is positioned to coordinate with active site metal ions, which is termed metal-binding pharmacophore (MBP). This review summarized the MBP data extracted from metalloenzyme-ligand interaction analyses, enumerated some classic MBPs, and analyzed the metalloenzyme selectivity and promiscuity. These information will provide clues and references for future innovative drug discovery targeting metalloenzymes.