{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T21:07:56Z","timestamp":1771362476705,"version":"3.50.1"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"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":[[2014,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Many of the nitroaromatic agents used in medicine function as prodrugs and must undergo activation before exerting their toxic effects. In most cases, this is catalyzed by flavin mononucleotide (FMN)-dependent type I nitroreductases (NTRs), a class of enzyme absent from higher eukaryotes but expressed by bacteria and several eukaryotic microbes, including trypanosomes and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>\n            . Here, we utilize this difference to evaluate whether members of a library of aziridinyl nitrobenzamides have activity against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania major<\/jats:named-content>\n            . Biochemical screens using purified\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. major<\/jats:named-content>\n            NTR (LmNTR) revealed that compounds containing an aziridinyl-2,4-dinitrobenzyl core were effective substrates for the enzyme and showed that the 4-nitro group was important for this activity. To facilitate drug screening against intracellular amastigote parasites, we generated leishmanial cells that expressed the luciferase reporter gene and optimized a mammalian infection model in a 96-well plate format. A subset of aziridinyl-2,4-dinitrobenzyl compounds possessing a 5-amide substituent displayed significant growth-inhibitory properties against the parasite, with the most potent agents generating 50% inhibitory concentrations of &lt;100 nM for the intracellular form. This antimicrobial activity was shown to be LmNTR specific since\n            <jats:italic>L. major NTR<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            heterozygote parasites were slightly resistance to most aziridinyl dinitrobenzyl agents tested. When the most potent leishmanicidal agents were screened against the mammalian cells in which the amastigote parasites were propagated, no growth-inhibitory effect was observed at concentrations of up to 100 \u03bcM. We conclude that the aziridinyl nitrobenzamides represent a new lead structure that may have the potential to treat leishmanial infections.\n          <\/jats:p>","DOI":"10.1128\/aac.01459-13","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T03:36:25Z","timestamp":1383017785000},"page":"370-377","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Evaluating Aziridinyl Nitrobenzamide Compounds as Leishmanicidal Prodrugs"],"prefix":"10.1128","volume":"58","author":[{"given":"Andrew A.","family":"Voak","sequence":"first","affiliation":[{"name":"Queen Mary Pre-Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Seifert","sequence":"additional","affiliation":[{"name":"Immunology and Infection Department, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuala A.","family":"Helsby","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shane R.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Queen Mary Pre-Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33945"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(02)90074-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000585"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2010.06.019"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.19.1.111-126.2006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/571242"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03630.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.27.100173.001533"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(00)00459-6"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1897\/02-220"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.05.016"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860050512"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030466"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/ges015"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.01.071"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/35016103"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/49.1.103"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1155\/S1110724303209098"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2007.08.005"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2009.08510_2.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.20137"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000923"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003326"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00722-13"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)50687-6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(66)90205-0"},{"key":"e_1_3_2_28_2","first-page":"2184","article-title":"Breakage of bacterial DNA by nitrofuran derivatives","volume":"31","author":"McCalla DR","year":"1971","unstructured":"McCallaDRReuversAKaiserC. 1971. 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