title: Repurposing the anti-malarial drug, quinacrine: new anti-colitis properties.
abstract: BACKGROUND
  Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with an increased risk of colorectal cancer in 8-10 years after disease onset. Current colitis treatment strategies do not offer a cure for the disease, but only treat the symptoms with limited success and dangerous side-effects. Also, there is no preventive treatment for either UC or colorectal cancer. Quinacrine is an anti-malarial drug with versatile use in the treatment of diseases involving inflammatory response such as rheumatoid arthritis and lupus erythematosus. It also has putative anti-cancer effect. Quinacrine's anti-inflammatory, anti-oxidant properties, and anti-tumorigenic properties make it a potential small molecule preventive agent for both UC and associated colorectal cancer.
  
  
  RESULTS
  There were obvious changes in the CDI, histology, and inflammatory load in quinacrine-treated groups in a dose and time dependent manner in both models of UC, induced by chemical or haptenating agent.
  
  
  METHODS
  We tested quinacrine at two different doses as a colitis treatment agent in two mouse models of UC - the dextran sulfate sodium and oxazolone. The clinical disease index (CDI), histological changes of the colon, levels of inflammatory markers (Cox-2, iNOS, p53) and overall health vitals were evaluated.
  
  
  CONCLUSIONS
  We demonstrate that quinacrine successfully suppresses colitis without any indication of toxicity or side-effects in two mouse models of UC.
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Chumanevich
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Witalison
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
authors.forename: Anusha
authors.initials: A
authors.lastname: Chaparala
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Chumanevich
authors.affiliation: School of Medicine, University of South Carolina, Columbia, SC, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Nagarkatti
authors.affiliation: School of Medicine, University of South Carolina, Columbia, SC, USA.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
authors.forename: Lorne J
authors.initials: LJ
authors.lastname: Hofseth
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D058492:Drug Repositioning; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010081:Oxazolone; D011796:Quinacrine / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000962:Antimalarials; D016159:Tumor Suppressor Protein p53; D010081:Oxazolone; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D011796:Quinacrine
keywords: colitis; dextran sulfate sodium; inflammation; oxazolone; quinacrine