{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:37:50Z","timestamp":1789911470016,"version":"4.0.1"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"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":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We report the results of a screen of a library of 925 potential prenyl synthase inhibitors against\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            farnesyl diphosphate synthase (TbFPPS) and against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. brucei<\/jats:named-content>\n            , the causative agent of human African trypanosomiasis. The most potent compounds were lipophilic analogs of the bone resorption drug zoledronate, some of which had submicromolar to low micromolar activity against bloodstream form\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. brucei<\/jats:named-content>\n            and selectivity indices of up to \u223c300. We evaluated the effects of two such inhibitors on survival and parasitemia in a\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. brucei<\/jats:named-content>\n            mouse model of infection and found that survival increased by up to 16 days. We also investigated the binding of three lipophilic bisphosphonates to an expressed TbFPPS using crystallography and investigated the thermodynamics of binding using isothermal titration calorimetry.\n          <\/jats:p>","DOI":"10.1128\/aac.01873-15","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T02:23:49Z","timestamp":1442888629000},"page":"7530-7539","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["<i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            Investigation of the Inhibition of Trypanosoma brucei Cell Growth by Lipophilic Bisphosphonates"],"prefix":"10.1128","volume":"59","author":[{"given":"Gyongseon","family":"Yang","sequence":"first","affiliation":[{"name":"Leishmania Research Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea"},{"name":"Interdisciplinary Programs of Functional Genomics, Yonsei University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuglae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of System Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Young","family":"Byun","sequence":"additional","affiliation":[{"name":"Leishmania Research Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gahee","family":"Choi","sequence":"additional","affiliation":[{"name":"Leishmania Research Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Seok","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of System Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Soo","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of System Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Oldfield","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hwan","family":"No","sequence":"additional","affiliation":[{"name":"Leishmania Research Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14694-6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.13.162"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2008.04.006"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3156.2001.00775.x"},{"key":"e_1_3_3_6_2","first-page":"190","article-title":"Innate lack of susceptibility of Ugandan Trypanosoma brucei rhodesiense to DL-alpha-difluoromethylornithine (DFMO)","volume":"46","author":"Iten M","year":"1995","unstructured":"Iten M, Matovu E, Brun R, Kaminsky R. 1995. 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