title: Dyes, trypanosomiasis and DNA: a historical and critical review.
abstract: Trypanosomiasis, a group of diseases including sleeping sickness in humans and Nagana in cattle in Africa, and Chagas' disease in South America, remains a considerable problem in the 21(st) century. The therapies that are available, however, usually have their roots in the "dye therapy" of a century ago, knowledge gained at the microscope from parasite staining procedures and converted to chemotherapy based on compounds closely related to the laboratory reagents. Dyes such as trypan red and trypan blue led to the development of suramin, while cationic nitrogen heterocyclic dyes furnished examples of the phenanthridinium class, such as ethidium (homidium) and isometamidium. Both suramin and isometamidium remain in use. Owing to mutagenicity issues, the presence of ethidium among the phenanthridinium dyes has led to concerns over the clinical use of related derivatives. There are several mechanisms for dye-DNA interaction, however, including possible hydrogen bonding of dye to the polymer, and these are discussed together with structure-activity relations and cellular localization of the phenanthridine and isomeric acridines involved. Better understanding of nucleic acid binding properties has allowed the preparation of more effective phenanthridinium analogues intended for use as anticancer/antiviral therapy.
authors.affiliation: School of Pharmacy & Biomolecular Science, Liverpool John Moores University, Liverpool, United Kingdom. mark_wainwright@hotmail.com
authors.forename: M
authors.initials: M
authors.lastname: Wainwright
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000266:history / Q000627:therapeutic use; D000349:Africa; D000818:Animals; D001391:Azo Compounds / Q000627:therapeutic use; D002417:Cattle; D014355:Chagas Disease / Q000188:drug therapy*; D004247:DNA / Q000737:chemistry*; D049672:History, 19th Century; D049673:History, 20th Century; D006801:Humans; D006860:Hydrogen Bonding; D007364:Intercalating Agents / Q000737:chemistry / Q000266:history / Q000627:therapeutic use; D010617:Phenanthridines / Q000737:chemistry* / Q000266:history / Q000627:therapeutic use*; D013020:South America; D013498:Suramin / Q000737:chemistry / Q000627:therapeutic use; D014343:Trypan Blue / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000266:history* / Q000627:therapeutic use; D014348:Trypanosoma congolense / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D000166:Acridines; D001391:Azo Compounds; D007364:Intercalating Agents; D010617:Phenanthridines; D014344:Trypanocidal Agents; C034943:trypan red; D013498:Suramin; D004247:DNA; D014343:Trypan Blue