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Available treatments present several limitations, with an increasing number of resistance cases. In the search for new chemotherapies, the natural product dehydrodieugenol B was used as a scaffold for the synthesis of a series of derivatives, resulting in the discovery of the promising analog [4-(4-(5-allyl-3-methoxy-2-((4-methoxybenzyl)oxy)phenoxy)-3-methoxybenzyl)morpholine,\n              <jats:bold>1<\/jats:bold>\n              ]. In this work, we investigated the effect of compound\n              <jats:bold>1<\/jats:bold>\n              on cell signaling in\n              <jats:italic>Leishmania (L.) infantum<\/jats:italic>\n              , culminating in cell death, as well as its immunomodulatory effect in the host cell. Additionally, we performed a pharmacokinetic profile study in an animal model. After treatment, compound\n              <jats:bold>1<\/jats:bold>\n              induced the alkalinization of acidocalcisomes and concomitant Ca\n              <jats:sup>2+<\/jats:sup>\n              release in the parasite. These events may induce depolarization of the mitochondrial potential, with successive collapse of the bioenergetic system, leading to a reduction of ATP and reactive oxygen species (ROS) levels. The analysis of total proteins and protein profile by matrix-assisted laser desorption ionization\u2013time of flight mass spectrometry (MALDI-TOF\/MS) demonstrated that compound\n              <jats:bold>1<\/jats:bold>\n              also altered the parasite proteins after treatment. Transmission electron microscopy studies revealed ultrastructural damage to mitochondria; together, these data suggest that compound\n              <jats:bold>1<\/jats:bold>\n              may promote autophagic cell death. Additionally, compound\n              <jats:bold>1<\/jats:bold>\n              also induced an immunomodulatory effect in host cells, with a reduction of Th1 and Th2 cytokine response, characterizing an anti-inflammatory compound. The obtained pharmacokinetic profile in rats enhances the potential of the compound, with a mean plasma half-life (T\n              <jats:sub>1\/2<\/jats:sub>\n              ) of 21 h. These data reinforce the potential of compound\n              <jats:bold>1<\/jats:bold>\n              as a new lead for future efficacy studies.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00831-24","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T13:00:27Z","timestamp":1728478827000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis of a dehydrodieugenol B derivative as a lead compound for visceral leishmaniasis\u2014mechanism of action and\n            <i>in vivo<\/i>\n            pharmacokinetic studies"],"prefix":"10.1128","volume":"68","author":[{"given":"Maiara","family":"Amaral","sequence":"first","affiliation":[{"name":"Laboratory of Physiopathology, Instituto Butantan, S\u00e3o Paulo, Brazil"},{"name":"Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}]},{"given":"Maiara M.","family":"Romanelli","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}]},{"given":"Hannah","family":"Asiki","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, United Kingdom"}]},{"given":"Joana","family":"Bicker","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal"},{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal"}]},{"given":"Daniela P.","family":"Lage","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa do Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}]},{"given":"Camila S.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa do Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}]},{"given":"Noemi N.","family":"Taniwaki","sequence":"additional","affiliation":[{"name":"Laboratory of Electron Microscopy, Instituto Adolfo Lutz, S\u00e3o Paulo, Brazil"}]},{"given":"Joao Henrique G.","family":"Lago","sequence":"additional","affiliation":[{"name":"Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, Brazil"}]},{"given":"Eduardo A. F.","family":"Coelho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa do Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"},{"name":"Departamento de Patologia Cl\u00ednica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}]},{"given":"Am\u00edlcar","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal"},{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6981-6639","authenticated-orcid":false,"given":"Ana","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal"},{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4149-0494","authenticated-orcid":false,"given":"Edward A.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, United Kingdom"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2559-7344","authenticated-orcid":true,"given":"Andre G.","family":"Tempone","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24213886"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00767-21"},{"key":"e_1_3_2_4_2","volume-title":"WHO guideline for the treatment of visceral leishmaniasis in HIV co-infected patients in East Africa and South-East Asia","author":"World Health Organization","year":"2022","unstructured":"World Health Organization. 2022. 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