{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:00:28Z","timestamp":1789610428158,"version":"build-2803163510"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2008,3,1]],"date-time":"2008-03-01T00:00:00Z","timestamp":1204329600000},"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":[[2008,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human African trypanosomiasis (HAT) is a fatal tropical disease caused by infection with protozoans of the species\n            <jats:italic>Trypanosoma brucei gambiense<\/jats:italic>\n            and\n            <jats:italic>T. b. rhodesiense<\/jats:italic>\n            . An oral prodrug, DB289, is a promising new therapy undergoing phase III clinical trials for early-stage HAT. DB289 is metabolically converted to the active trypanocidal diamidine DB75 [2,5-bis(4-amidinophenyl)furan]. We previously determined that DB75 inhibits yeast mitochondrial function (C. A. Lanteri, B. L. Trumpower, R. R. Tidwell, and S. R. Meshnick, Antimicrob. Agent Chemother. 48:3968-3974, 2004). The purpose of this study was to investigate if DB75 targets the mitochondrion of\n            <jats:italic>T. b. brucei<\/jats:italic>\n            bloodstream forms. DB75 rapidly accumulates within the mitochondria of living trypanosomes, as indicated by the fluorescent colocalization of DB75 with a mitochondrion-specific dye. Fluorescence-activated cell sorting analysis of rhodamine 123-stained living trypanosomes shows that DB75 and other trypanocidal diamidines (pentamidine and diminazene) collapse the mitochondrial membrane potential. DB75 inhibits ATP hydrolysis within\n            <jats:italic>T. brucei<\/jats:italic>\n            mitochondria and appears to inhibit the oligomycin-sensitive F\n            <jats:sub>1<\/jats:sub>\n            F\n            <jats:sub>0<\/jats:sub>\n            -ATPase and perhaps other ATPases. DB75 is most likely not an inhibitor of electron transport within trypanosome mitochondria, since DB75 fails to inhibit mitochondrial respiration when glycerol-3-phosphate is used as the respiratory substrate. However, DB75 inhibits whole-cell respiration (50% inhibitory concentration, 20 \u03bcM) at drug concentrations and incubation durations that also result in the dissipation of the mitochondrial membrane potential. Taken together, these findings suggest that the mitochondrion is a target of the trypanocidal action of DB75.\n          <\/jats:p>","DOI":"10.1128\/aac.00642-07","type":"journal-article","created":{"date-parts":[[2007,12,18]],"date-time":"2007-12-18T02:39:01Z","timestamp":1197945541000},"page":"875-882","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":70,"title":["The Mitochondrion Is a Site of Trypanocidal Action of the Aromatic Diamidine DB75 in Bloodstream Forms of\n            <i>Trypanosoma brucei<\/i>"],"prefix":"10.1128","volume":"52","author":[{"given":"Charlotte A.","family":"Lanteri","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Tidwell","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Meshnick","sequence":"additional","affiliation":[{"name":"Departments of Microbiology &amp; Immunology and Epidemiology, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(00)00303-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14694-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(83)90118-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb18118.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1472-8206.2003.00167.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(96)00557-4"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.5.1.45-53.2006"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.47.28153"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)84639-2"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"12283","DOI":"10.1073\/pnas.93.22.12283","volume":"93","year":"1996","unstructured":"Coury, J. 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