{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T03:16:22Z","timestamp":1772766982026,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T00:00:00Z","timestamp":1555459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Traditional antimalarial drugs based on 4\u2010aminoquinolines have exhibited good antiproliferative activities against <jats:italic>Leishmania<\/jats:italic> parasites; however, their clinical use is currently limited. To identify new 4\u2010aminoquinolines to combat American cutaneous leishmaniasis, we carried out a full in vitro evaluation of a series of dehydroxy isoquines and isotebuquines against two <jats:italic>Leishmania<\/jats:italic> parasites such as <jats:italic>Leishmania braziliensis<\/jats:italic> and <jats:italic>Leishmania mexicana<\/jats:italic>. First, the antiproliferative activity of the quinolines was studied against the promastigote forms of <jats:italic>L. braziliensis<\/jats:italic> and <jats:italic>L. mexicana<\/jats:italic> parasites, finding that five of them exhibited good antileishmanial responses with micromolar IC<jats:sub>50<\/jats:sub> values ranging from 3.84 to 10\u2009\u03bcM. A structure\u2010activity relationship analysis gave evidence that a piperidine or a morpholine attached as <jats:italic>N<\/jats:italic>\u2010alkyamino terminal substituent as well as the inclusion of an extra phenyl ring attached at the aniline ring of the isotebuquine core constitute important pharmacophores to generate the most active derivatives, with antileishmanial responses by far superior to those found for the reference drug, glucantime. All compounds showed a relatively low toxicity on human dermis fibroblasts, with CC<jats:sub>50<\/jats:sub> ranging from 69 to &gt;250\u2009\u03bcM. The five most active compounds displayed moderate to good antileishmanial activity against the intracellular amastigote form of <jats:italic>L. braziliensis<\/jats:italic>, compared to the reference drug. In particular, compound <jats:bold>2j<\/jats:bold> was identified as the most potent agent against antimony\u2010resistant amastigotes of <jats:italic>L. braziliensis<\/jats:italic> with acceptable biological response and selectivity, emerging as a promising candidate for further in vivo antileishmanial evaluation. Diverse mechanism\u2010of\u2010action studies and molecular docking simulations were performed for the most active 4\u2010aminoquinoline.<\/jats:p>","DOI":"10.1002\/ardp.201800281","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T18:36:58Z","timestamp":1555526218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Identification of dehydroxy isoquine and isotebuquine as promising antileishmanial agents"],"prefix":"10.1002","volume":"352","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8747-5153","authenticated-orcid":false,"given":"Angel H.","family":"Romero","sequence":"first","affiliation":[{"name":"C\u00e1tedra de Qu\u00edmica, Facultad de Farmacia Universidad Central de Venezuela  Caracas Venezuela"},{"name":"Laboratorio de Ingenier\u00eda Gen\u00e9tica, Instituto de Biomedicina, Facultad de Medicina Universidad Central de Venezuela  Caracas Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noris","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratorio de Ingenier\u00eda Gen\u00e9tica, Instituto de Biomedicina, Facultad de Medicina Universidad Central de Venezuela  Caracas Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sim\u00f3n E.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Florida Gainesville Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Oviedo","sequence":"additional","affiliation":[{"name":"Laboratorio de Ingenier\u00eda Gen\u00e9tica, Instituto de Biomedicina, Facultad de Medicina Universidad Central de Venezuela  Caracas Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,17]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2007.06.009"},{"key":"e_1_2_6_1_3_1","first-page":"255","volume":"45","author":"Sharma U.","year":"2008","journal-title":"J. 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