Bismuth antiulcer complexes

Abstract

Bismuth compounds have been widely used in medicine for more than 200 years, and new bismuth-containing drugs are now being developed. However, the biological chemistry of bismuth is poorly understood. In this review, the use of Bi(III) in antiulcer and antibacterial agents is described, as well as in anti-HIV and radiotherapeutic agents. Bi(III) exhibits a highly variable coordination number and coordination geometry, and alkoxide ligands can induce a strong stereochemical ‘lone-pair effect’. The chemistry of Bi(III) carboxylates and aminocarboxylates is dominated by intermolecular interactions which lead to polymeric structures. Bi(III) binds strongly to the thiolate sulfur of the tripeptide glutathione, but these adducts are also kinetically labile which allows rapid translocation of Bi(III) inside cells. The major biological target for Bi(III) appears to be proteins and not DNA. Bi(III) can bind to both Zn(II) sites (e.g. metallothionein) and Fe(III) sites (e.g. transferrin and lactoferrin) in proteins and enzymes. The mechanism of its antibacterial and antimicrobial activity may therefore involve interference with both Fe(III) and Zn(II) pathways. Further work is needed to understand the mechanism of action of bismuth and provide a basis for the design of more effective drugs.