{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:47:21Z","timestamp":1790380041702,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2014K1A4A7A01074645"],"award-info":[{"award-number":["NRF-2014K1A4A7A01074645"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Leishmaniasis is a disease caused by pathogenic\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>\n                    parasites; current treatments are toxic and expensive, and drug resistance has emerged. While pentamidine, a diamidine-type compound, is one of the treatments, its antileishmanial mechanism of action has not been investigated in depth. Here we tested several diamidines, including pentamidine and its analog DB75, against\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania donovani<\/jats:named-content>\n                    and elucidated their antileishmanial mechanisms. We identified three promising new antileishmanial diamidine compounds with 50% effective concentrations (EC\n                    <jats:sub>50<\/jats:sub>\n                    s) of 3.2, 3.4, and 4.5 \u03bcM, while pentamidine and DB75 exhibited EC\n                    <jats:sub>50<\/jats:sub>\n                    s of 1.46 and 20 \u03bcM, respectively. The most potent antileishmanial inhibitor, compound 1, showed strong DNA binding properties, with a shift in the melting temperature (\u0394\n                    <jats:italic>\n                      T\n                      <jats:sub>m<\/jats:sub>\n                    <\/jats:italic>\n                    ) of 24.2\u00b0C, whereas pentamidine had a \u0394\n                    <jats:italic>\n                      T\n                      <jats:sub>m<\/jats:sub>\n                    <\/jats:italic>\n                    value of 2.1\u00b0C, and DB75 had a \u0394\n                    <jats:italic>\n                      T\n                      <jats:sub>m<\/jats:sub>\n                    <\/jats:italic>\n                    value of 7.7\u00b0C. Additionally, DB75 localized in\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. donovani<\/jats:named-content>\n                    kinetoplast DNA (kDNA) and mitochondria but not in nuclear DNA (nDNA). For 2 new diamidines, strong localization signals were observed in kDNA at 1 \u03bcM, and at higher concentrations, the signals also appeared in nuclei. All tested diamidines showed selective and dose-dependent inhibition of kDNA, but not nDNA, replication, likely by inhibiting\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. donovani<\/jats:named-content>\n                    topoisomerase IB. Overall, these results suggest that diamidine antileishmanial compounds exert activity by accumulating toward and blocking replication of parasite kDNA.\n                  <\/jats:p>","DOI":"10.1128\/aac.01129-16","type":"journal-article","created":{"date-parts":[[2016,9,6]],"date-time":"2016-09-06T23:03:57Z","timestamp":1473203037000},"page":"6828-6836","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Antileishmanial Mechanism of Diamidines Involves Targeting Kinetoplasts"],"prefix":"10.1128","volume":"60","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":"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":"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_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2006.06.012"},{"key":"e_1_3_2_3_2","volume-title":"Fact sheet N375 leishmaniasis","author":"WHO","year":"2015","unstructured":"WHO. 2015. Fact sheet N375 leishmaniasis. 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Topoisomerase research of kinetoplastid parasite Leishmania, with special reference to development of therapeutics. 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