{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:27:10Z","timestamp":1758709630932},"reference-count":56,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"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":[[2015,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Leishmaniasis is the protozoan disease second in importance for human health, superseded only by malaria; however, the options for chemotherapeutic treatment are increasingly limited due to drug resistance and toxicity. Under this perspective, a quest for new chemical compounds is urgently needed. An N-substituted 2-aminoalkan-1-ol scaffold has been shown to be a versatile scaffold for antiparasitic activity. Knowledge about its mechanism of action is still rather limited. In this work, we endeavored to define the leishmanicidal profile of such \u03b2-amino alkanol derivatives using a set of 15 N-mono- and disubstituted surrogates, tested on\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            promastigotes and intracellular amastigotes. The best compound (compound 5), 2-ethylaminododecan-1-ol, had a 50% effective concentration (EC\n            <jats:sub>50<\/jats:sub>\n            ) of 0.3 \u03bcM and a selectivity index of 72 for infected THP-1 cells and was selected for further elucidation of its leishmanicidal mechanism. It induced fast depletion of intracellular ATP content in promastigotes in the absence of vital dye intracellular entry, ruling out plasma membrane permeabilization as its origin. Confocal and transmission electron microscopy analyses showed that compound 5 induced severe mitochondrial swelling and vesiculation. Polarographic analysis using an oxygen electrode demonstrated that complex II of the respiratory chain (succinate reductase) was strongly inhibited by compound 5, identifying this complex as one of the primary targets. Furthermore, for other \u03b2-amino alkanols whose structures differed subtly from that of compound 5, plasma membrane permeabilization or interference with membrane traffic was also observed. In all, N-substituted \u03b2-amino alkanols were shown as appealing leishmanicidal candidates deserving further exploration.\n          <\/jats:p>","DOI":"10.1128\/aac.04003-14","type":"journal-article","created":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T05:47:07Z","timestamp":1418104027000},"page":"1211-1218","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Mechanisms of Action of Substituted \u03b2-Amino Alkanols on Leishmania donovani"],"prefix":"10.1128","volume":"59","author":[{"given":"Mar\u00eda \u00c1ngeles","family":"Abeng\u00f3zar","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas (CIB-CSIC), Unidad Metabol\u00f3mica, Interacciones y Bioan\u00e1lisis (UMIB), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis A.","family":"Bustos","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Farmac\u00e9utica, Facultad de Farmacia, CIETUS, IBSAL, Universidad de Salamanca, Salamanca, Spain"},{"name":"Departamento de Ciencias Farmac\u00e9uticas, Facultad de Ciencias, Universidad Cat\u00f3lica del Norte, Antofagasta, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Garc\u00eda-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez-Neyra (IPBLN-CSIC), Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Fern\u00e1ndez de Palencia","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas (CIB-CSIC), Unidad Metabol\u00f3mica, Interacciones y Bioan\u00e1lisis (UMIB), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Escarcena","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Farmac\u00e9utica, Facultad de Farmacia, CIETUS, IBSAL, Universidad de Salamanca, Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santiago","family":"Castanys","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez-Neyra (IPBLN-CSIC), Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"del Olmo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Farmac\u00e9utica, Facultad de Farmacia, CIETUS, IBSAL, Universidad de Salamanca, Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Gamarro","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez-Neyra (IPBLN-CSIC), Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo","family":"San Feliciano","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Farmac\u00e9utica, Facultad de Farmacia, CIETUS, IBSAL, Universidad de Salamanca, Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Rivas","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas (CIB-CSIC), Unidad Metabol\u00f3mica, Interacciones y Bioan\u00e1lisis (UMIB), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03630.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-011-2555-5"},{"key":"e_1_3_3_5_2","first-page":"411","article-title":"Drug resistance mechanisms in clinical isolates of Leishmania donovani","volume":"123","author":"Singh N","year":"2006","unstructured":"Singh N. 2006. 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