Infections caused by resistant organisms: Could organic arsenic compounds be an effective treatment?

Abstract

Without question one of the most important medicinal chemistry discoveries of the 20th century was made by Paul Ehrlich and his colleagues, chemist, Alfred Bertheim and bacteriologist, Sahachiro Hata. They ushered in the age of targeted chemotherapy in 1910 with the discovery of the anti-syphilitic organic arsenic agent, arsphenamine or Salvarsan (also known as 606). It was the clinical compound of choice for treating syphilis until penicillin and other antibiotics were introduced clinically in the 1940s. Yet now, more than 100years after its discovery, the precise biochemical mechanism by which this compound eliminates the syphilis spirochete in vivo from humans and animals remains unknown. Other organic arsenic compounds such as melarsoprol and roxarson have been used to treat parasitic infections. More recently, arsenic trioxide has been shown effective in producing remissions and possibly cures in a high percentage of patients with acute promyelocytic leukemia. However, the exact biochemical mechanism by which this clinical result is manifested remains to be determined. The purpose of this publication is to propose a possible mechanism, by which these apparently diverse arsenic compounds function to produce their clinical results and to suggest their potential for the treatment of infections caused by resistant organisms.