Basis of bismuth antiulcer drugs: biological chemistry and pharmacology

Abstract

Bismuth compounds have been used in medicine for centuries and there is potential for the design of new bismuth drugs. The biological chemistry of bismuth was not attracted attention until recently. The widely used bismuth citrate antiulcer drugs are polymers, which could be deposited on the ulcer crater forming a protective coating. The major biological target for bismuth appears to be proteins and enzymes. It can bind to both zinc(II) and iron(III) sites in proteins and the mechanism of antimicrobial activity may therefore involve interference with zinc and iron(III) pathways. There have been no documented cases of bismuth toxicity with the recommended acute dosage of either bismuth citrate (CBS or RBC) or bismuth subsalicylate. The complete genome sequence of Helicobacter Pylori will facilitate the understanding of the mechanism of action of bismuth and also provide a basis for the design of new bismuth antiulcer drugs.

鉍的化合物在醫學中應用已超過二百年,但其生物化學并沒有深入系統的研究,直到近年來才逐漸引起重視。枸椽酸鉍的結構表明其治療潰瘍有賴于在酸性條件下的超分子結構,枸椽酸鉍超分子和潰瘍膜表面的相互作用對其生物活性起著重要作用,同樣重要的是鉍和蛋白質及酶的相互作用。鉍可以結合在蛋白中鐵和鋅的位置,和其傳輸及抑制細菌生長有關,詳細機理仍有待進一步研究。鉍在人體中的吸收極低,大部分是由腎臟通過尿液排出。“幽門螺桿菌”（Helicobacter pylori）基因組的測定,將有助于了解鉍劑的作用機理,并為設計新型鉍劑奠定基礎。