Warner Victor D, Soloway Albert H
James L. Winkle College of Pharmacy, University of Cincinnati, USA.
College of Pharmacy of The Ohio State University, USA.
Med Hypotheses. 2017 Jul;104:78-79. doi: 10.1016/j.mehy.2017.05.026. Epub 2017 May 26.
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.
毫无疑问，20世纪最重要的药物化学发现之一是由保罗·埃尔利希及其同事——化学家阿尔弗雷德·贝特海姆和细菌学家秦佐八郎做出的。1910年，他们发现了抗梅毒有机砷剂胂凡纳明（也称为洒尔佛散，亦称作606），从而开创了靶向化疗时代。在20世纪40年代青霉素及其他抗生素临床应用之前，它一直是治疗梅毒的首选临床化合物。然而，在其发现100多年后的现在，该化合物在人和动物体内消除梅毒螺旋体的确切生化机制仍不为人知。其他有机砷化合物，如美拉胂醇和罗沙胂，已被用于治疗寄生虫感染。最近，三氧化二砷已被证明对高比例的急性早幼粒细胞白血病患者有效，可实现病情缓解甚至可能治愈。然而，这一临床效果得以显现的确切生化机制仍有待确定。本出版物的目的是提出一种可能的机制，通过该机制这些明显不同的砷化合物发挥作用以产生其临床效果，并表明它们在治疗由耐药生物体引起的感染方面的潜力。
