{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:05:32Z","timestamp":1790744732709,"version":"4.1.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T00:00:00Z","timestamp":1343088000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0001734","type":"journal-article","created":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T21:33:45Z","timestamp":1343165625000},"page":"e1734","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Pharmacology of DB844, an Orally Active aza Analogue of Pafuramidine, in a Monkey Model of Second Stage Human African Trypanosomiasis"],"prefix":"10.1371","volume":"6","author":[{"given":"John K.","family":"Thuita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Z.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Kagira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrine L.","family":"Denton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary F.","family":"Paine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond E.","family":"Mdachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace A.","family":"Murilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley","family":"Ching","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Boykin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Tidwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto","family":"Brun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1172\/JCI33945","article-title":"Kinetoplastids: related protozoan pathogens, different diseases.","volume":"118","author":"K Stuart","year":"2008","journal-title":"J Clin Invest"},{"key":"ref2","article-title":"Civil conflict and sleeping sickness in Africa in general and Uganda in particular.","volume":"1","author":"LB Ford","year":"2007","journal-title":"Confl Hlth"},{"key":"ref3","article-title":"Human African trypanosomiasis.","author":"R Brun","year":"2009","journal-title":"Lancet"},{"key":"ref4","article-title":"African Trypanosomiasis (sleeping sickness).","year":"2010"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1371\/journal.pmed.0050055","article-title":"Eliminating human African trypanosomiasis: where do we stand and what comes next?","volume":"5","author":"PP Simarro","year":"2008","journal-title":"PLoS Med"},{"key":"ref6","first-page":"e1007","article-title":"The Human African Trypanosomiasis Control and Surveillance Programme of the World Health Organization 2000\u20132009: The Way Forward.","volume":"5","author":"PP Simarro","year":"2011","journal-title":"PLoS NTDs"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"e1008","DOI":"10.1371\/journal.pntd.0001008","article-title":"Sleeping Sickness Elimination in Sight: Time to celebrate and reflect, but not relax.","volume":"5","author":"S Aksoy","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0140-6736(09)61117-X","article-title":"Nifurtimox-eflornithine combination therapy for second-stage African <italic>Trypanosoma brucei gambiense<\/italic> trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial.","volume":"374","author":"G Priotto","year":"2009","journal-title":"Lancet"},{"key":"ref9","first-page":"876","article-title":"Diamidines for human African trypanosomiasis. Curr Opin Invest.","volume":"11","author":"MF Paine","year":"2010","journal-title":"Drugs"},{"key":"ref10","article-title":"Efficacy of the diamidine DB75 and its prodrug DB289, against murine models of human African trypanosomiasis. Acta Trop Oct 108: 6\u201310.","volume":"5","author":"JK Thuita","year":"2008","journal-title":"Epub 2008 Aug"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.1128\/AAC.00225-09","article-title":"New treatment option for second-stage African sleeping sickness: In vitro and in vivo efficacy of aza analogs of DB289.","volume":"53","author":"T Wenzler","year":"2009","journal-title":"Antimicrob Agents and Chemother"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1128\/AAC.00831-08","article-title":"Efficacy of a novel diamidine compound 2, 5-bis (4-amidinophenyl)-furan-bis-O-methlylamidoxime (Pafuramidine, DB289) against <italic>T. b rhodesiense<\/italic> infection in vervet monkeys after oral administration.","volume":"53","author":"RE Mdachi","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/00498250500087671","article-title":"In vitro metabolism of an orally active O-methyl amidoxime prodrug for the treatment of CNS trypanosomiasis.","volume":"35","author":"JH Ansede","year":"2005","journal-title":"Xenobiotica"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/1439-7633(20010803)2:7\/8<559::AID-CBIC559>3.0.CO;2-U","article-title":"Novel dications with unfused aromatic systems: Trithiophene and Trifuran derivatives of furimidazoline.","volume":"2","author":"P Bilik","year":"2001","journal-title":"Chem Bio Chem"},{"key":"ref15","first-page":"414","article-title":"Dicationic DNA minor groove binders as antimicrobial agents.","author":"RR Tidwell","year":"2003"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1128\/AAC.00192-06","article-title":"Accumulation and intracellular distribution of antitrypanosomal diamidine compounds DB75 and DB820 in African trypanosomes.","volume":"50","author":"AM Mathis","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.1021\/jm0302602","article-title":"Synthesis and anti-protozoal activity of aza-analogues of furamidine.","volume":"46","author":"MA Ismail","year":"2003","journal-title":"J Med Chem"},{"key":"ref18","first-page":"173","article-title":"Pre-clinical testing of potential trypanocidal drugs in primates: preliminary investigation of an experimental diamidine in vervets.","author":"E Fink","year":"1980"},{"key":"ref19","first-page":"255","article-title":"<italic>T. b. rhodesiense<\/italic> infection in vervet monkeys. II. Provocation of the encephalitic late phase by treatment of infected monkeys.","volume":"33","author":"H Schmidt","year":"1982","journal-title":"Tropenmed Parasitol"},{"key":"ref20","first-page":"795","article-title":"Animal models of CNS (second-stage) sleeping sickness.","author":"C Gichuki","year":"1999"},{"key":"ref21","first-page":"e238","article-title":"<italic>Trypanosoma brucei rhodesiense<\/italic> transmitted by a single tsetse fly bite in vervet monkeys as a model of Human African Trypanosomiasis.","volume":"2","author":"JK Thuita","year":"2008","journal-title":"PloS NTD"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1124\/dmd.106.010587","article-title":"CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O-demethylation of the antiparasitic prodrug DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime].","volume":"34","author":"MZ Wang","year":"2006","journal-title":"Drug Metab Dispos"},{"key":"ref23","first-page":"124","article-title":"Total protein and white cell changes in the cerebrospinal fluid of vervet monkeys infected with <italic>Trypanosoma rhodesiense<\/italic> and post-treatment reaction.","volume":"4","author":"JM Ndung'u","year":"1994","journal-title":"J Protozool Res"},{"key":"ref24","article-title":"Guidance document on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluation","year":"2000"},{"key":"ref25","first-page":"384","article-title":"The haematocrit centrifuge technique for the diagnosis of African trypanosomiasis.","volume":"27","author":"PT Woo","year":"1970","journal-title":"Acta Trop"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/0014-4894(76)90110-7","article-title":"<italic>Trypanosoma brucei<\/italic>: a rapid \u2018matching\u2019 method for estimating the host&apos;s parasitaemia.","volume":"40","author":"WJ Herbert","year":"1976","journal-title":"Exp Parasitol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0035-9203(00)90327-4","article-title":"Single centrifugation of cerebrospinal fluid in a sealed pasteur pipette for simple, rapid, and sensitive detection of trypanosomes.","volume":"94","author":"TW Miezan","year":"2000","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1128\/AAC.00250-10","article-title":"Novel arylimidamides for treatment of visceral leishmaniasis.","volume":"54","author":"MZ Wang","year":"2010","journal-title":"Antimocrob Agents Chemother"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1124\/dmd.105.005017","article-title":"Unusual dehydroxylation of antimicrobial amidoxime prodrugs by cytochrome b5 and NADH cytochrome b5 reductase.","volume":"33","author":"JY Saulter","year":"2005","journal-title":"Drug Metab Dispos"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1128\/AAC.42.3.666","article-title":"Anti-Pneumocystis activities of aromatic diamidoxime prodrugs.","volume":"42","author":"JE Hall","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"key":"ref31","first-page":"183","article-title":"IgG and IgM Levels in serum and CSF of <italic>T. rhodesiense<\/italic>-infected vervet monkeys.","volume":"7","author":"E Fink","year":"1983","journal-title":"Contrib Microbiol Immunol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1046\/j.1365-3024.1998.00164.x","article-title":"Nitric oxide production in vervet monkeys (<italic>Cercopithecus aethiops<\/italic>) infected with <italic>Trypanosoma brucei<\/italic>.","volume":"20","author":"JM Sternberg","year":"2002","journal-title":"Parasit Immunol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/BF00612951","article-title":"The pathogenesis of trypanosomiasis of the CNS: studies on parasitological and neurohistological findings in <italic>Trypanosoma rhodesiense<\/italic> infected vervet monkeys.","volume":"399","author":"H Schmidt","year":"1983","journal-title":"Virchows Arch [Pathol Anat]"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1124\/dmd.106.013391","article-title":"Pharmacokinetics and metabolism of the prodrug DB289 (2,5-bis[4-(<italic>n<\/italic>-methoxyamidino)phenyl]furan monomaleate) in rat and monkey and its conversion to the antiprotozoal\/antifungal drug DB75 (2,5-bis(4-guanylphenyl)furan dihydrochloride).","volume":"35","author":"I Midgley","year":"2007","journal-title":"Drug Metab Dispos"},{"key":"ref35","article-title":"Treatment of African trypanosomosis with DB75: pharmacokinetics, relapses and cross resistance.","author":"SC Bernhard","year":"2006"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1128\/AAC.00192-06","article-title":"Accumulation and intracellular distribution of antitrypanosomal diamidine compounds DB75 and DB820 in African trypanosomes.","volume":"50","author":"AM Mathis","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1124\/jpet.108.149872","article-title":"Pentamidine Movement across the Murine Blood-Brain and Blood-Cerebrospinal Fluid Barriers: Effect of Trypanosome Infection, Combination Therapy, P-Glycoprotein, and Multidrug Resistance-Associated Protein.","volume":"329","author":"L Sanderson","year":"2009","journal-title":"J Pharm Exp Ther"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1128\/CMR.00007-10","article-title":"Penetration of drugs through the blood-cerebrospinal fluid\/blood-brain barrier for Treatment of Central Nervous system infections Clin.","volume":"23","author":"R Nau","year":"2010","journal-title":"Microbiol Rev"},{"key":"ref39","first-page":"59","article-title":"Haematology of experimental <italic>Trypanosoma brucei rhodesiense<\/italic> infection in vervet monkeys.","volume":"13","author":"JM Kagira","year":"2006","journal-title":"Afr J Hlth Sci"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3201\/eid0801.010130","article-title":"African trypanosomiasis in travellers returning to the United Kingdom.","volume":"8","author":"DA Moore","year":"2002","journal-title":"Emerg Infect Dis"},{"issue":"10","key":"ref41","doi-asserted-by":"crossref","first-page":"pii\u200a=\u200a20111","DOI":"10.2807\/ese.17.10.20111-en","article-title":"Human African trypanosomiasis in a Belgian traveller returning from the Masai Mara area, Kenya.","volume":"17","author":"J Clerinx","year":"2012","journal-title":"Euro Surveill"},{"key":"ref42","first-page":"505","article-title":"Anaemia in human African trypanosomiasis caused by <italic>Trypanosoma brucei rhodesiense<\/italic>.","volume":"81","author":"JE Chisi","year":"2004","journal-title":"East Afric Med J"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1182\/blood.V95.6.2157","article-title":"Scavenger receptors on liver Kupffer cells mediate the in vivo uptake of oxidatively damaged red blood cells in mice.","volume":"95","author":"V Terpstra","year":"2000","journal-title":"Blood"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1124\/jpet.105.090407","article-title":"Primaquine-induced hemolytic anemia: role of splenic macrophages in the fate of 5-hydroxyprimaquine-treated rat erythrocytes.","volume":"315","author":"ZS Bowman","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"key":"ref45","first-page":"290","article-title":"Comparative evaluation of hepatotoxic side effects of various new trypanocidal diamidines in rat hepatocytes and mice.","volume":"40","author":"H Sippel","year":"1990","journal-title":"Arzneimitteforshung"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/j.1600-0773.1991.tb01314.x","article-title":"Influence of pentamidine and two new trypanocidal agents (DAPI, DIPI) on liver metabolism of mice.","volume":"69","author":"U Steinmann","year":"1991","journal-title":"Pharmacol Toxicol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0163-7258(95)00012-6","article-title":"Inhibition of mitochondrial \u00df-oxidation as a mechanism of hepatotoxicity.","volume":"67","author":"B Fromenty","year":"1995","journal-title":"Pharmacol Ther"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/toxsci\/65.2.166","article-title":"Mechanisms of hepatotoxicity.","volume":"65","author":"H Jaeschke","year":"2002","journal-title":"Toxicol Sci"}],"container-title":["PLoS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0001734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T09:56:25Z","timestamp":1743846985000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0001734"}},"subtitle":[],"editor":[{"given":"Jayne","family":"Raper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,7,24]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2012,7,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0001734","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,24]]}}}