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In order to identify new potent anticancer agents based on 4\u2010aminoquinoline, we evaluated the antiproliferative activity of a series of dehydroxy isoquines and isotebuquines against five human cancer lines. HeLa and <jats:styled-content style=\"fixed-case\">SKB<\/jats:styled-content>r3 were significantly more sensitive to the action of tested quinolines than the A549, <jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>\u20107, and <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>\u20103 cancer lines. Compound <jats:bold>2h<\/jats:bold> was by far the most potent derivative against four of the tested lines (except to <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>3 line), exhibiting low micromolar or nanomolar <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> values superior to adriamycin reference, low toxicities on dermis human fibroblasts (<jats:styled-content style=\"fixed-case\">LD<\/jats:styled-content><jats:sub>50<\/jats:sub>\u00a0&gt;\u00a0250\u00a0\u03bcM), and excellent selectivity indexes against the mentioned cancer cells. A structure\u2013activity relationship analysis put in evidence that a pyrrolidine or morpholine moiety as <jats:italic>N<\/jats:italic>\u2010alkyl terminal substitution and the incorporation of the extra phenyl attached to aniline ring are pharmacophore essentials for improvement the anticancer activity of the studied dehydroxy isoquines and isotebuquines. From the results, compound <jats:bold>2h<\/jats:bold> emerged as a promising anticancer candidate for further in vitro assays against resistant\u2010strain and in vivo studies as well as pharmacokinetic and genotoxicity studies. Mechanistic assays suggested that the most active quinoline <jats:bold>2h<\/jats:bold> act as calcium\u2010activated potassium channel activator.<\/jats:p>","DOI":"10.1111\/cbdd.13461","type":"journal-article","created":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T14:20:51Z","timestamp":1545315651000},"page":"638-646","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of dehydroxy isoquine and isotebuquine as promising anticancer agents targeting K+ channel"],"prefix":"10.1111","volume":"93","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"}],"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":"Francisco","family":"Arvelo","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Institutos de Estudios Avanzados \u2010IDEA \u00c1rea Salud  Caracas Venezuela"},{"name":"Laboratorio de Cultivo de Tejidos y Biolog\u00eda de Tumores Instituto de Biolog\u00eda Experimental\u2010IBE Facultad de Ciencias\u2010UCV  Caracas Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Sojo","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Institutos de Estudios Avanzados \u2010IDEA \u00c1rea Salud  Caracas Venezuela"},{"name":"Laboratorio de Cultivo de Tejidos y Biolog\u00eda de Tumores Instituto de Biolog\u00eda Experimental\u2010IBE Facultad de Ciencias\u2010UCV  Caracas Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Calderon","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda y Biof\u00edsica Centro de Biolog\u00eda Celular Instituto de Biolog\u00eda Experimental\u2010IBE Facultad de Ciencias UCV  Caracas Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Morales","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Cl\u00ednica Santa Mar\u00eda Cevalfes  Caracas Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,2,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.07.044"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2009.04.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm200046z"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2005.04.003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(02)00111-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2005.12.017"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042698399"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.11171"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2014.12.008"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00047a008"},{"key":"e_1_2_8_12_1","unstructured":"Dinsmore C. 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