Chemistry of Bismuth in Medicine

Abstract

Bismuth(III) compounds such as bismuth subsalicylate (Pepto-Bismol®), colloidal bismuth subcitrate (De-Nol®, Lizhudele®) and ranitidine bismuth citrate (Tritec®, Pylorid®) have long been used in medicine for the treatment of a variety of diseases (1,2). Bismuth drugs in combination with antibiotics as a quadruple therapy show excellent successful rate in the eradication of H. pylori even for antibiotic resistance strains (3). We have demonstrated that Bi(III) drugs tend to form polymeric structures (and in fact a MOF structure) and interfere with zinc/iron homeostasis in pathogens whereas has no toxicity towards humans (4,5). Using an integrative metalloproteomics approach, we identified UreG as a new drug target for H. pylori and discover that bismuth compounds including those used clinically of Bi(III) compounds can effectively tame the superbugs through inhibition of metallo-β-lactamase (MBL) (6,7). Importantly, we demonstrate that Bi(III) exhibits potential as broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing antibiotics such as carbapenems. We also show that certain bismuth compounds can reduce the side-effect of cisplatin through induction of key proteins in vivo. A strcuture-activity-relationship will be discussed. We thank the Research Grants Council of Hong Kong SAR (17305415, 17333616 and 17307017), the Innovation Technology Commission of Hong Kong SAR (ITS/124/17) and the Norman & Cecelia Yip Fund for support.