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Existing drugs are limited due to cost, toxicity, declining efficacy and unavailability in endemic places. Drug repurposing has established as an efficient way for the discovery of drugs for a variety of diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>The objective of the present work was testing the antileishmanial activity of thioridazine, an antipsychotic agent with demonstrated effect against other intracellular pathogens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The cytotoxicity for mouse peritoneal macrophages as well as the activity against\n                      <jats:italic>Leishmania amazonensis<\/jats:italic>\n                      ,\n                      <jats:italic>Leishmania mexicana<\/jats:italic>\n                      and\n                      <jats:italic>Leishmania major<\/jats:italic>\n                      promastigotes and intracellular amastigotes, as well as in a mouse model of cutaneous leishmaniasis, were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thioridazine inhibited the\n                      <jats:italic>in vitro<\/jats:italic>\n                      proliferation of promastigotes (50% inhibitory concentration\u2014IC\n                      <jats:sub>50<\/jats:sub>\n                      \u2014values in the range of 0.73\u00a0\u00b5M to 3.8\u00a0\u00b5M against\n                      <jats:italic>L. amazonensis<\/jats:italic>\n                      ,\n                      <jats:italic>L. mexicana<\/jats:italic>\n                      and\n                      <jats:italic>L. major<\/jats:italic>\n                      ) and intracellular amastigotes (IC\n                      <jats:sub>50<\/jats:sub>\n                      values of 1.27\u00a0\u00b5M to 4.4\u00a0\u00b5M for the same species). In contrast, in mouse peritoneal macrophages, the 50% cytotoxic concentration was 24.0\u2009\u00b1\u20091.89\u00a0\u00b5M. Thioridazine inhibited the growth of cutaneous lesions and reduced the number of parasites in the infected tissue of mice. The dose of thioridazine that inhibited lesion development by 50% compared to controls was 23.3\u2009\u00b1\u20093.1\u00a0mg\/kg and in terms of parasite load, it was 11.1\u2009\u00b1\u20090.97\u00a0mg\/kg.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Thioridazine was effective against the promastigote and intracellular amastigote stages of three\n                      <jats:italic>Leishmania<\/jats:italic>\n                      species and in a mouse model of cutaneous leishmaniasis, supporting the potential repurposing of this drug as an antileishmanial agent.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11686-023-00746-2","type":"journal-article","created":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T04:01:55Z","timestamp":1702094515000},"page":"324-331","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In Vitro and In Vivo Antileishmanial Activity of Thioridazine"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-8648","authenticated-orcid":false,"given":"Sergio","family":"Sifontes-Rodr\u00edguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5137-0253","authenticated-orcid":false,"given":"Niurka","family":"Mollineda-Diogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-809X","authenticated-orcid":false,"given":"Lianet","family":"Monzote-Fidalgo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-2939","authenticated-orcid":false,"given":"Alma Reyna","family":"Escalona-Monta\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4742-2783","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"Escario Garc\u00eda-Trevijano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-3429","authenticated-orcid":false,"given":"Mar\u00eda Magdalena","family":"Aguirre-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-4989","authenticated-orcid":false,"given":"Alfredo","family":"Meneses-Marcel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,12,9]]},"reference":[{"issue":"4","key":"746_CR1","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1093\/labmed\/lmac134","volume":"54","author":"BA Mathison","year":"2023","unstructured":"Mathison BA, Bradley BT (2023) Review of the clinical presentation, pathology, diagnosis, and treatment of leishmaniasis. 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Sergio Sifontes Rodr\u00edguez was supported by a UNAM-DGAPA Postdoctoral fellowship 2021\u20132022 (Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The experimental protocol was approved by the Institutional Ethics Committee for the Care and Use of Laboratory Animals of the Center of Bioactive Chemicals (CBQ\/CEAE\/2021.4). All animal experiments complied with the ARRIVE guidelines and were carried out in accordance with the International Council for Laboratory Animal Science (ICLAS) ethical guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}