Bioinorganic Chemistry of Bismuth and Antimony:  Target Sites of Metallodrugs

Abstract

The biocoordination chemistry of antimony and bismuth has been extensively investigated due to the historical use of these metals in medicine. Structures of bismuth antiulcer agents and interactions of Bi3+ with proteins and enzymes, such as transferrin and lactoferrin, the histidine-rich protein Hpn, and urease, have been characterized. Sb5+ is a prodrug and is bioreduced or activated to its active form Sb3+ intracellularly. Antimony binds to biomolecules, such as glutathione, trypanothione, and nucleotides, and forms binary and ternary complexes, which may allow it to be trafficked in cells. These studies have improved our understanding of the mechanism of action of bismuth and antimony drugs, which in turn allows the future design of drugs.

A Histidine-rich and Cysteine-rich Metal-binding Domain at the C Terminus of Heat Shock Protein A from Helicobacter pylori

“…Previously, we characterized the structure of CBS, the recognition of Bi 3ϩ by the iron and zinc storage proteins, and recently the histidine-rich protein Hpn (20,34,(51)(52)(53). Using a metalloproteomic approach, we screened both Ni 2ϩ -and Bi 3ϩ -binding proteins in H. pylori.…”

“…Although the antimicrobial activity of bismuth against H. pylori has been demonstrated (19), the mechanism of the action is not well understood. A number of proteins and enzymes have been demonstrated previously as intracellular targets of bismuth (20). Using a metalloproteomic approach, it was found that intracellular levels of four proteins (HspA, HspB, NapA, and TsaA) were significantly up-or down-regulated after bismuth treatment (21), and thus bismuth-binding proteins in H. pylori were identified.…”

Metal‐Binding Properties of an Hpn‐Like Histidine‐Rich Protein

“…Under highly acidic conditions, the activities of urease in the wild-type strain increased three times compared with those in the mutant strains, thereby supporting the idea of Hisrich proteins (Hpn and Hpnl) as nickel reservoirs. [15] Hpnl protein, which consists of a histidine-rich domain and two glutamine-rich motifs (Figure 1), [16] was previously Abstract: The Hpn-like protein (Hpnl), a histidine-and glutamine-rich protein, is critical for Helicobacter pylori colonization in human gastric muscosa. In this study, the thermodynamic properties of Ni II , Cu II , Co II , and Zn II toward Hpnl were studied by isothermal titration calorimetry (ITC).…”

Anticancer Activity of Molecular Compounds of Arsenic, Antimony and Bismuth

“…Various antimony compounds find continued use in the treatment of tropical diseases, most notably leishmaniasis caused by Leishmania species, which are human protozoan parasites of the trypanosomatidae family [50][51][52][53][54]. The two most prominent antimony compounds used in the treatment of cutaneous and visceral leishmaniasis are sodium stibogluconate (XIX, Pentostam) and meglumine antimonate (XX, Glucantime): their molecular compositions let alone precise molecular structures remain uncertain [55].…”