{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:02:16Z","timestamp":1784721736743,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo State Research Support Foundation","doi-asserted-by":"publisher","award":["2018\/18954-4"],"award-info":[{"award-number":["2018\/18954-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo State Research Support Foundation","doi-asserted-by":"publisher","award":["2020\/03399-5"],"award-info":[{"award-number":["2020\/03399-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Brazilian National Research Council","doi-asserted-by":"publisher","award":["404478\/2025-5"],"award-info":[{"award-number":["404478\/2025-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Brazilian National Research Council","doi-asserted-by":"publisher","award":["2024\/22547-6"],"award-info":[{"award-number":["2024\/22547-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Brazilian National Research Council","doi-asserted-by":"publisher","award":["2023\/18327-8"],"award-info":[{"award-number":["2023\/18327-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Brazilian National Research Council","doi-asserted-by":"publisher","award":["88887.162302\/2025-00"],"award-info":[{"award-number":["88887.162302\/2025-00"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective anti-Toxoplasma gondii agents. This study investigated the antiparasitic potential of loratadine, a second-generation antihistamine, using an integrated in silico, in vitro, and in vivo approach. The anti-T. gondii activity of loratadine was evaluated through \u03b2-galactosidase-based proliferation assays, reversibility assays, and experiments using pretreated tachyzoites. In vivo efficacy was assessed in murine models of acute and chronic toxoplasmosis. Disease progression, survival, parasite burden, and cerebral cyst formation were analyzed following treatment. Loratadine inhibited the intracellular proliferation of T. gondii tachyzoites in a concentration-dependent manner and induced partially irreversible effects on parasite viability after drug withdrawal. Pretreatment of extracellular tachyzoites produced limited effects, suggesting that loratadine predominantly acts during the intracellular stage of infection. In the acute toxoplasmosis model, loratadine treatment delayed disease progression, prolonged animal survival, and significantly reduced the number of tachyzoites recovered from the peritoneal cavity. In the chronic infection model, treatment significantly decreased both the number and size of cerebral cysts, although these findings do not demonstrate cyst eradication or direct bradyzoite killing. Despite its measurable biological activity, loratadine exhibited a relatively low in vitro selectivity index, highlighting the need for further optimization. These exploratory findings identify loratadine as a promising lead compound (hit) for further optimization rather than an immediately translatable therapeutic candidate. Additional medicinal chemistry, pharmacokinetic, mechanistic, and confirmatory preclinical studies will be required to determine its potential for anti-T. gondii drug development.<\/jats:p>","DOI":"10.3390\/pathogens15070773","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:48:28Z","timestamp":1784717308000},"page":"773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the Anti-Toxoplasma gondii Potential of Loratadine"],"prefix":"10.3390","volume":"15","author":[{"given":"Stephanie Ortega","family":"Alves","sequence":"first","affiliation":[{"name":"Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (Lab. PARASITTOS), Faculdade de Medicina de Jundia\u00ed, Jundia\u00ed 13202-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid de Oliveira","family":"Dias","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (Lab. PARASITTOS), Faculdade de Medicina de Jundia\u00ed, Jundia\u00ed 13202-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1256-057X","authenticated-orcid":false,"given":"Gabriel Candido","family":"Moura","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (Lab. PARASITTOS), Faculdade de Medicina de Jundia\u00ed, Jundia\u00ed 13202-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1978-1658","authenticated-orcid":false,"given":"Samuel Cota","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-320, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4418-0838","authenticated-orcid":false,"given":"Juliana Quero","family":"Reim\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (Lab. PARASITTOS), Faculdade de Medicina de Jundia\u00ed, Jundia\u00ed 13202-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mar\u00edn-Garc\u00eda, P.-J., Planas, N., and Llobat, L. (2022). Toxoplasma gondii in foods: Prevalence, control, and safety. Foods, 11.","DOI":"10.3390\/foods11162542"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e44881","DOI":"10.1097\/MD.0000000000044881","article-title":"Toxoplasmosis in pregnancy: Analysis of maternal seropositivity in a large cohort in Turkey and clinical consequences of neonates","volume":"104","author":"Yuruk","year":"2025","journal-title":"Medicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00057-17","DOI":"10.1128\/CMR.00057-17","article-title":"Treatment of toxoplasmosis: Historical perspective, animal models, and current clinical practice","volume":"31","author":"Dunay","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"117956","DOI":"10.1016\/j.biopha.2025.117956","article-title":"Chemotherapy against Toxoplasma gondii: A bibliometric analysis of in vitro and mouse model studies (2015\u20132024)","volume":"186","author":"Evangelista","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"118057","DOI":"10.1016\/j.ejmech.2025.118057","article-title":"Novel indole-based marinoquinolines as promising candidates against Toxoplasma gondii","volume":"299","author":"Torres","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"30773","DOI":"10.1038\/s41598-025-04772-0","article-title":"Improving computational drug repositioning through multi-source disease similarity networks","volume":"15","author":"Le","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00036","DOI":"10.1016\/j.fawpar.2019.e00036","article-title":"Treatment of toxoplasmosis: Current options and future perspectives","volume":"15","author":"Konstantinovic","year":"2019","journal-title":"Food Waterborne Parasitol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"350","DOI":"10.2165\/00002018-199410050-00002","article-title":"H1-receptor antagonists","volume":"10","author":"Simons","year":"1994","journal-title":"Drug Saf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1039\/D3OB02091F","article-title":"Clemastine\/tamoxifen hybrids as easily accessible antileishmanial drug leads","volume":"22","author":"Agostino","year":"2024","journal-title":"Org. Biomol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Say\u00e9, M., Gauna, L., Valera-Vera, E., Reigada, C., Miranda, M.R., and Pereira, C.A. (2020). Crystal violet structural analogues identified by in silico drug repositioning present anti-Trypanosoma cruzi activity through inhibition of proline transporter TcAAAP069. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0007481"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"30816","DOI":"10.1038\/s41598-025-89434-x","article-title":"Discovery of clocinizine as a potential oral drug against Schistosoma mansoni infection","volume":"15","author":"Castro","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yong, H., Di, L., Wang, Z., Yang, J., Yang, P., and Gao, X. (2025). Efficacy and safety of combined loratadine and mometasone furoate therapy in allergic rhinitis patients. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1560295"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1248\/bpb.27.1630","article-title":"Classification of loratadine based on the biopharmaceutics drug classification concept and possible in vitro\u2013in vivo correlation","volume":"27","author":"Khan","year":"2004","journal-title":"Biol. Pharm. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1046\/j.1365-2222.1999.0290s3147.x","article-title":"Loratadine: A non-sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation","volume":"29","author":"Kay","year":"1999","journal-title":"Clin. Exp. Allergy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1021\/ci800305f","article-title":"OSIRIS, an entirely in-house developed drug discovery informatics system","volume":"49","author":"Sander","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-4939-9857-9_5","article-title":"Assays for monitoring Toxoplasma gondii infectivity in the laboratory mouse","volume":"2071","author":"Wang","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.placenta.2012.12.006","article-title":"Trophoblast cells are able to regulate monocyte activity to control Toxoplasma gondii infection","volume":"34","author":"Castro","year":"2013","journal-title":"Placenta"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"de Oliveira, R.M., Lima dos Santos, N.C., Almeida, M.P.O., Lima J\u00fanior, J.P.D., Souza, G.D., Barbosa, M.C., Faria, G.V., Paschoalino, M., Alves, R.N., and Gomes, A.O. (2025). Novel drug candidates targeting Toxoplasma gondii in maternal\u2013fetal interface models. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1673462"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1128\/AAC.41.9.1849","article-title":"Use of Toxoplasma gondii expressing beta-galactosidase for colorimetric assessment of drug activity in vitro","volume":"41","author":"McFadden","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.ejmech.2017.10.013","article-title":"Pt(II), Pd(II) and Au(III) complexes with a thiosemicarbazone derived from diacetylmonooxime: Structural analysis, trypanocidal activity, cytotoxicity and first insight into the antiparasitic mechanism of action","volume":"141","author":"Carneiro","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31147","DOI":"10.1021\/acsomega.5c05130","article-title":"Phenotypic screening of the MMV Global Health Priority Box identifies selective compounds with anti-Toxoplasma gondii activity","volume":"10","author":"Moura","year":"2025","journal-title":"ACS Omega"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1128\/iai.63.7.2549-2555.1995","article-title":"Sex-determined resistance to Toxoplasma gondii is associated with temporal differences in cytokine production","volume":"63","author":"Roberts","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Diethelm, L.T.H., Ramos, A.B.d.S.B., de Lorena, G.B., Trajano, B.I., do Esp\u00edrito Santo, R.D., de Menezes, R.P.B., Scotti, M.T., Colombo, F.A., Marques, M.J., and Correia, C.R.D. (2024). First description of marinoquinoline derivatives\u2019 activity against Toxoplasma gondii. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16020262"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1021\/acsinfecdis.4c00689","article-title":"High-throughput repurposing screen reveals compounds with activity against Toxoplasma gondii bradyzoites","volume":"11","author":"Uddin","year":"2025","journal-title":"ACS Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"107369","DOI":"10.1016\/j.micpath.2025.107369","article-title":"Repurposing astemizole to kill multidrug-resistant bacteria isolated in general surgery","volume":"200","author":"Cao","year":"2025","journal-title":"Microb. Pathog."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"125639","DOI":"10.1016\/j.ijpharm.2025.125639","article-title":"Topical loratadine-loaded invasomal gel repurposed for vulvovaginal candidiasis: In vitro, in silico, ex vivo, and in vivo studies","volume":"677","author":"Abdelmonem","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Navarrete-Carriola, D.V., Rivera, G., Ortiz-P\u00e9rez, E., Paz-Gonz\u00e1lez, A.D., Mart\u00ednez-V\u00e1zquez, A.V., Aquino-Gonz\u00e1lez, L.V., Argueta-Figueroa, L., Doyle, M.P., and Moreno-Rodr\u00edguez, A. (2025). Antiparasitic effect of polyphenols and terpenes from natural products against Trypanosoma cruzi and Leishmania mexicana. Metabolites, 15.","DOI":"10.3390\/metabo15080560"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1080\/07420520802257646","article-title":"Circadian time-effect of orally administered loratadine on plasma pharmacokinetics in mice","volume":"25","author":"Dridi","year":"2008","journal-title":"Chronobiol. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.1007\/s00436-018-6027-z","article-title":"Activities of anti-Toxoplasma drugs and compounds against tissue cysts in the last three decades (1987 to 2017): A systematic review","volume":"117","author":"Montazeri","year":"2018","journal-title":"Parasitol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.anl.2022.01.014","article-title":"Medical Management of Rhinitis in Pregnancy","volume":"49","author":"Gupta","year":"2022","journal-title":"Auris Nasus Larynx"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/7\/773\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:15:50Z","timestamp":1784718950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/7\/773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["pathogens15070773"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15070773","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}