{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:02:48Z","timestamp":1774976568546,"version":"3.50.1"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human African trypanosomiasis (HAT, also called sleeping sickness), a neglected tropical disease endemic to sub-Saharan Africa, is caused by the parasites\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trypanosoma brucei gambiense<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. brucei rhodesiense<\/jats:named-content>\n            . Current drugs against this disease have significant limitations, including toxicity, increasing resistance, and\/or a complicated parenteral treatment regimen. DB829 is a novel aza-diamidine that demonstrated excellent efficacy in mice infected with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. b. rhodesiense<\/jats:named-content>\n            or\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. b. brucei<\/jats:named-content>\n            parasites. The current study examined the pharmacokinetics,\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            activity against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. b. gambiense<\/jats:named-content>\n            , and time of drug action of DB829 in comparison to pentamidine. DB829 showed outstanding\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy in mice infected with parasites of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. b. gambiense<\/jats:named-content>\n            strains, despite having higher\n            <jats:italic>in vitro<\/jats:italic>\n            50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) than against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. b. rhodesiense<\/jats:named-content>\n            strain STIB900. A single dose of DB829 administered intraperitoneally (5 mg\/kg of body weight) cured all mice infected with different\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. b. gambiense<\/jats:named-content>\n            strains. No cross-resistance was observed between DB829 and pentamidine in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. b. gambiense<\/jats:named-content>\n            strains isolated from melarsoprol-refractory patients. Compared to pentamidine, DB829 showed a greater systemic exposure when administered intraperitoneally, partially contributing to its improved efficacy. Isothermal microcalorimetry and\n            <jats:italic>in vivo<\/jats:italic>\n            time-to-kill studies revealed that DB829 is a slower-acting trypanocidal compound than pentamidine. A single dose of DB829 (20 mg\/kg) administered intraperitoneally clears parasites from mouse blood within 2 to 5 days. In summary, DB829 is a promising preclinical candidate for the treatment of first- and second-stage HAT caused by both\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trypanosoma brucei<\/jats:named-content>\n            subspecies.\n          <\/jats:p>","DOI":"10.1128\/aac.00398-13","type":"journal-article","created":{"date-parts":[[2013,8,20]],"date-time":"2013-08-20T01:58:37Z","timestamp":1376963917000},"page":"5330-5343","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Pharmacokinetics, Trypanosoma brucei gambiense Efficacy, and Time of Drug Action of DB829, a Preclinical Candidate for Treatment of Second-Stage Human African Trypanosomiasis"],"prefix":"10.1128","volume":"57","author":[{"given":"Tanja","family":"Wenzler","sequence":"first","affiliation":[{"name":"Medical Parasitology &amp; Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihyung","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence, Kansas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Braissant","sequence":"additional","affiliation":[{"name":"Laboratory of Biomechanics and Biocalorimetry (LOB2), Faculty of Medicine, University of Basel, Basel, Switzerland"},{"name":"Department of Urology, University Hospital Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Boykin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Georgia State University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reto","family":"Brun","sequence":"additional","affiliation":[{"name":"Medical Parasitology &amp; Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Zhuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence, Kansas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1712.110921"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050055"},{"key":"e_1_3_3_4_2","first-page":"1","article-title":"Control and surveillance of African trypanosomiasis. 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