{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:01:30Z","timestamp":1792807290290,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T00:00:00Z","timestamp":1677283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Apoio a Pesquisa do Estado da Para\u00edba (FAPESQ)\/CAPES","award":["23038.004264\/2015-03"],"award-info":[{"award-number":["23038.004264\/2015-03"]}],"id":[{"id":"https:\/\/ror.org\/021y4b202","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Leishmaniasis is a neglected tropical infectious disease with thousands of cases annually; it is of great concern to global health, particularly the most severe form, visceral leishmaniasis. Visceral leishmaniasis treatments are minimal and have severe adverse effects. As guanidine-bearing compounds have shown antimicrobial activity, we analyzed the cytotoxic effects of several guanidine-bearing compounds on Leishmania infantum in their promastigote and amastigote forms in vitro, their cytotoxicity in human cells, and their impact on reactive nitrogen species production. LQOFG-2, LQOFG-6, and LQOFG-7 had IC50 values of 12.7, 24.4, and 23.6 \u00b5M, respectively, in promastigotes. These compounds exhibited cytotoxicity in axenic amastigotes at 26.1, 21.1, and 18.6 \u00b5M, respectively. The compounds showed no apparent cytotoxicity in cells from healthy donors. To identify mechanisms of action, we evaluated cell death processes by annexin V and propidium iodide staining and nitrite production. Guanidine-containing compounds caused a significant percentage of death by apoptosis in amastigotes. Independent of L. infantum infection, LQOFG-7 increased nitrite production in peripheral blood mononuclear cells, which suggests a potential mechanism of action for this compound. Therefore, these data suggest that guanidine derivatives are potential anti-microbial molecules, and further research is needed to fully understand their mechanism of action, especially in anti-leishmanial studies.<\/jats:p>","DOI":"10.3390\/tropicalmed8030141","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:04:11Z","timestamp":1677463451000},"page":"141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Leishmanicidal Activity of Guanidine Derivatives against Leishmania infantum"],"prefix":"10.3390","volume":"8","author":[{"given":"Fernanda Silva","family":"Almeida","sequence":"first","affiliation":[{"name":"Immunology of Infectious Diseases Laboratory of Department of Cellular and Molecular Biology; Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"},{"name":"Biotechnology Doctoral Program, Rede Nordeste de Biotecnologia, Universidade Federal da Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor Partite","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Fine Organic Chemistry Lab, School of Sciences and Technology, S\u00e3o Paulo State University (UNESP), Presidente Prudente 19060-080, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edson dos Santos","family":"Silva","sequence":"additional","affiliation":[{"name":"Immunology of Infectious Diseases Laboratory of Department of Cellular and Molecular Biology; Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4924-0542","authenticated-orcid":false,"given":"Leonardo Lima","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Immunology of Infectious Diseases Laboratory of Department of Cellular and Molecular Biology; Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9323-7677","authenticated-orcid":false,"given":"Pedro Henrique","family":"de Sousa Palmeira","sequence":"additional","affiliation":[{"name":"Immunology of Infectious Diseases Laboratory of Department of Cellular and Molecular Biology; Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8445-5189","authenticated-orcid":false,"given":"Luiz Henrique Agra","family":"Cavalcante-Silva","sequence":"additional","affiliation":[{"name":"Immunology of Infectious Diseases Laboratory of Department of Cellular and Molecular Biology; Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dem\u00e9trius A. M. de","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Universidade Federal da Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian P. G. do","family":"Amaral","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Cellular and Molecular Biology; Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1348-8554","authenticated-orcid":false,"given":"Eduardo Ren\u00e9 P\u00e9rez","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Fine Organic Chemistry Lab, School of Sciences and Technology, S\u00e3o Paulo State University (UNESP), Presidente Prudente 19060-080, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0964-389X","authenticated-orcid":false,"given":"Tatjana S. L.","family":"Keesen","sequence":"additional","affiliation":[{"name":"Immunology of Infectious Diseases Laboratory of Department of Cellular and Molecular Biology; Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.jinf.2014.07.016","article-title":"Leishmaniasis","volume":"69","author":"Pace","year":"2014","journal-title":"J. Infect."},{"key":"ref_2","unstructured":"(2022, April 15). Leishmaniasis. Available online: https:\/\/www.who.int\/health-topics\/leishmaniasis#tab=tab_1."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.idc.2018.10.005","article-title":"Visceral Leishmaniasis: Recent Advances in Diagnostics and Treatment Regimens","volume":"33","author":"Diro","year":"2019","journal-title":"Infect. Dis. Clin. N. 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