{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:57:23Z","timestamp":1780549043105,"version":"3.54.1"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T00:00:00Z","timestamp":1529539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Instituto de Biomedicina Dr. Jacinto Convit"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Trifluoromethyl\u2010substituted quinolones and their analogues have emerged as an interesting platform in the last 6 years to design antiparasite agents. Many of their derivatives have been demonstrated to display excellent efficacy against flagellate parasites such as <jats:italic>Plasmodium<\/jats:italic> spp. In order to identify new analogues of trifluoromethyl\u2010substituted quinolones to treat the American cutaneous leishmaniasis, we evaluated the antiproliferative activity of a series of 2\u2010(trifluoromethyl)benzo[<jats:italic>b<\/jats:italic>]\u2010[1,8]naphthyridin\u20104(1<jats:italic>H<\/jats:italic>)\u2010ones on the <jats:italic>Leishmania braziliensis<\/jats:italic> and <jats:italic>Leishmania mexicana<\/jats:italic> parasites. The mentioned derivatives have never been evaluated against any parasite strain. In general, an <jats:italic>in vitro<\/jats:italic> evaluation on <jats:italic>L<\/jats:italic>.(<jats:italic>L<\/jats:italic>)<jats:italic>mexicana<\/jats:italic> and <jats:italic>L<\/jats:italic>.(<jats:italic>V<\/jats:italic>)<jats:italic>braziliensis<\/jats:italic> showed that <jats:italic>L<\/jats:italic>.(<jats:italic>L<\/jats:italic>)<jats:italic>mexicana<\/jats:italic> was more sensitive to the action of the compounds than <jats:italic>L<\/jats:italic>.(<jats:italic>V<\/jats:italic>)<jats:italic>braziliensis<\/jats:italic>, either in the promastigote or in the amastigote form. Five compounds exhibited moderate efficacy against <jats:italic>L<\/jats:italic>.(<jats:italic>L<\/jats:italic>)<jats:italic>mexicana<\/jats:italic> promastigotes, with IC<jats:sub>50<\/jats:sub> values ranging from 9.65 to 14.76\u2009\u00b5M. From the mentioned molecules, three compounds, <jats:bold>1e<\/jats:bold>, <jats:bold>1f<\/jats:bold>, and <jats:bold>1h<\/jats:bold>, showed a discrete response against axenic and intracellular amastigotes, with LD<jats:sub>50<\/jats:sub> values between 19 and 24\u2009\u00b5M. Moreover, an <jats:italic>in vitro<\/jats:italic> evaluation was performed on an antimony\u2010resistant amastigote strain and a human isolate amastigote strain. These three compounds showed discrete toxicity on peritoneal macrophages; however, their relatively good antiamastigote response compared to the drug glucantime promoted our trifluoromethyl\u2010substituted benzo[<jats:italic>b<\/jats:italic>][1,8]naphthyridin\u20104(1<jats:italic>H<\/jats:italic>)\u2010ones as a potential platform to design potent antileishmanial agents.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ardp.201800094","type":"journal-article","created":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T09:38:33Z","timestamp":1529573913000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antileishmanial activity, structure\u2013activity relationship of series of 2\u2010(trifluoromethyl)benzo[<i>b<\/i>][1,8]naphthyridin\u20104(1<i>H<\/i>)\u2010ones"],"prefix":"10.1002","volume":"351","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8747-5153","authenticated-orcid":false,"given":"Angel H.","family":"Romero","sequence":"first","affiliation":[{"name":"Laboratorio de Ingenier\u00eda Gen\u00e9tica, Instituto de Biomedicina, Facultad de Medicina Universidad Central de Venezuela, San Luis Caracas Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon E.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Florida Gainesville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, San Luis Caracas Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Oviedo","sequence":"additional","affiliation":[{"name":"Laboratorio de Ingenier\u00eda Gen\u00e9tica, Instituto de Biomedicina, Facultad de Medicina Universidad Central de Venezuela, San Luis Caracas Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio837"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2007.06.009"},{"key":"e_1_2_6_4_1","first-page":"255","volume":"45","author":"Sharma U.","year":"2008","journal-title":"J. Vector Borne Dis"},{"key":"e_1_2_6_5_1","unstructured":"\u201cLeishmaniasis Fact sheet No. 375.\u201d World Health Organization. January2014."},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03635.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/22.1.1"},{"key":"e_1_2_6_8_1","unstructured":"World Health Organization. (http:\/\/www.who.int\/leishmaniasis\/en\/)."},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2011.01.006"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.inhe.2009.12.005"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2011.0642"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/617521"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2003.09.008"},{"key":"e_1_2_6_13_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2014.04.003"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2005.02.007"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03630.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.4.859"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00515"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm5000408"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13588-014-0010-1"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.11.1860"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(02)00013-5"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(01)80107-4"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.07.081"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.03.020"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.01.022"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2017.03.008"},{"key":"e_1_2_6_25_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2017.07.013"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfluchem.2014.10.014"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/00397911.2015.1135956"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00053a011"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm200015a"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400246e"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm500147k"},{"key":"e_1_2_6_29_3","doi-asserted-by":"publisher","DOI":"10.1021\/jm201642z"},{"key":"e_1_2_6_29_4","doi-asserted-by":"publisher","DOI":"10.1021\/jm500942v"},{"key":"e_1_2_6_29_5","doi-asserted-by":"publisher","DOI":"10.1021\/jm200718m"},{"key":"e_1_2_6_29_6","doi-asserted-by":"publisher","DOI":"10.1021\/jm201184h"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00548-09"},{"key":"e_1_2_6_31_1","doi-asserted-by":"crossref","first-page":"907","DOI":"10.4049\/jimmunol.151.2.907","volume":"151","author":"Evans T. G.","year":"1993","journal-title":"J. Immunol"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.141.7.2407"},{"key":"e_1_2_6_32_1","unstructured":"http:\/\/www.cambridgesoft.com\/Ensemble_for_Chemistry\/ChemBioDraw\/ChemBio(DrawUltra14Suite."},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(96)00423-1"},{"key":"e_1_2_6_34_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/B978-012369520-8.50005-X","volume-title":"Drug\u2010Like Properties: Concepts, Structure Design and Methods: From ADME to Toxicity Optimization","author":"Kerns E.","year":"2008"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020017n"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(90)90187-Z"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(91)90104-5"},{"key":"e_1_2_6_38_1","unstructured":"Graph Pad Prism Software Inc. 4.02 for windows. May 17th 1992\u20132004. [4] M. A. Thompson ArgusLab 4.0 Planaria Software LLC Seatle WA 2004."}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fardp.201800094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.201800094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T09:52:17Z","timestamp":1694944337000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.201800094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,21]]},"references-count":48,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1002\/ardp.201800094"],"URL":"https:\/\/doi.org\/10.1002\/ardp.201800094","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,21]]},"assertion":[{"value":"2018-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1800094"}}