Chemical structure of bismuth compounds determines their gastric ulcer healing efficacy and anti-Helicobacter pylori activity

The recognition of the role of Helicobacter pylori in the pathogenesis of p eptic ulcer disease has led to renewed interest in bismuth pharmacology sin ce bismuth compounds have both anti-Helicobacter pylori and ulcer healing p roperties. The precise chemical structure of current bismuth compounds is n ot known. This has hindered the development of new and potentially more eff icacious formulations. We have created two new compounds, 2-chloro-1,3-dith ia-2-bismolane (CDTB) and 1,2-[bis(1,3-dithia-2-bismolane)thio]ethane (BTBT ), with known structure. In a rat model of gastric ulceration, BTBT was com parable to, and CDTB was significantly less effective than colloidal bismut h subcitrate in healing cryoprobe induced ulcers. However, both BTBT and CD TB inhibited H. pylori growth in vitro at concentrations <1/10 that of coll oidal bismuth subcitrate. The effects on ulcer healing are not mediated by suppression of acid secretion, pepsin inhibition, or prostaglandin producti on. Since all treated animals received the same amount of elemental bismuth , it appears that the efficacy of bismuth compounds varies with compound st ructure and is not simply dependent on the delivery of bismuth ion. Because the structure of the novel compounds is known, our understanding of the re lationship of bismuth compound structure and to biologic activity will incr ease. In the future it may be possible to design other novel bismuth compou nds with more potent anti-H. pylori and ulcer healing effects.