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The incidence of human leishmaniasis has increased over the past decades due to failing prevention and therapeutic measures\u2014there are no vaccines and chemotherapy, which is problematic. Acridine derivatives constitute an interesting group of nitrogen-containing heterocyclic compounds associated with numerous bioactivities, with emphasis to their antileishmanial potential. The present work builds on computational studies focusing on a specific enzyme of the parasite, S-adenosylmethionine decarboxylase (AdoMet DC), with several 1,2,3,4-tetrahydro-acridines emerging as potential inhibitors, evidencing this scaffold as a promising building block for novel antileishmanial pharmaceuticals. Thus, several 1,2,3,4-tetrahydroacridine derivatives have been synthesized, their activity against Leishmania (Leishmania) infantum promastigotes evaluated and a structure\u2013activity relationship (SAR) study was developed based on the results obtained. Even though the majority of the 1,2,3,4-tetrahydroacridines evaluated presented high levels of toxicity, the structural information gathered in this work allowed its application with another scaffold (quinoline), leading to the obtention of N1,N12-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine (12) as a promising novel antileishmanial agent (IC50 = 0.60 \u00b1 0.11 \u03bcM, EC50 = 11.69 \u00b1 3.96 \u03bcM and TI = 19.48).<\/jats:p>","DOI":"10.3390\/pharmaceutics15020669","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T04:51:46Z","timestamp":1676523106000},"page":"669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Structure\u2013Activity Relationship Studies of 9-Alkylamino-1,2,3,4-tetrahydroacridines against Leishmania (Leishmania) infantum Promastigotes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4538-1527","authenticated-orcid":false,"given":"Carlos F. M.","family":"Silva","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8794-8950","authenticated-orcid":false,"given":"Teresa","family":"Le\u00e3o","sequence":"additional","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"ICBAS, School of Medicine and Biomedical Sciences, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Filipa","family":"Dias","sequence":"additional","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"ICBAS, School of Medicine and Biomedical Sciences, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Ana M.","family":"Tom\u00e1s","sequence":"additional","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"ICBAS, School of Medicine and Biomedical Sciences, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4249-7089","authenticated-orcid":false,"given":"Diana C. G. A.","family":"Pinto","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Eduardo F. T.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6594-6022","authenticated-orcid":false,"given":"Ana","family":"Oliveira","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2748-4722","authenticated-orcid":false,"given":"Pedro A.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-8286","authenticated-orcid":false,"given":"Artur M. S.","family":"Silva","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2010). First WHO Report on Neglected Tropical Diseases: Working to Overcome the Global Impact of Neglected Tropical Diseases, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.7861\/clinmedicine.19-2-157","article-title":"Neglected Tropical Diseases: Elimination and Eradication","volume":"19","author":"Bodimeade","year":"2019","journal-title":"Clin. Med."},{"key":"ref_3","unstructured":"World Health Organization (WHO) (2010). 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