{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:25:42Z","timestamp":1790814342282,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNPq (the National Council of Research of Brazil)","award":["308755\/2018-9"],"award-info":[{"award-number":["308755\/2018-9"]}]},{"name":"CNPq (the National Council of Research of Brazil)","award":["E26\/203.246\/2017"],"award-info":[{"award-number":["E26\/203.246\/2017"]}]},{"name":"CNPq (the National Council of Research of Brazil)","award":["E-26\/010.001861\/2019"],"award-info":[{"award-number":["E-26\/010.001861\/2019"]}]},{"name":"CNPq (the National Council of Research of Brazil)","award":["E-26\/211.025\/2019"],"award-info":[{"award-number":["E-26\/211.025\/2019"]}]},{"name":"FAPERJ (Research Support Foundation of the State of Rio de Janeiro)","award":["308755\/2018-9"],"award-info":[{"award-number":["308755\/2018-9"]}]},{"name":"FAPERJ (Research Support Foundation of the State of Rio de Janeiro)","award":["E26\/203.246\/2017"],"award-info":[{"award-number":["E26\/203.246\/2017"]}]},{"name":"FAPERJ (Research Support Foundation of the State of Rio de Janeiro)","award":["E-26\/010.001861\/2019"],"award-info":[{"award-number":["E-26\/010.001861\/2019"]}]},{"name":"FAPERJ (Research Support Foundation of the State of Rio de Janeiro)","award":["E-26\/211.025\/2019"],"award-info":[{"award-number":["E-26\/211.025\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/objectives: Schistosomiasis is caused by flatworms of the genus Schistosoma, for which mollusks of the genus Biomphalaria are intermediate hosts. Niclosamide (NCL) is a molluscicide recommended by the World Health Organization (WHO) for control of Biomphalaria. Although effective, it is expensive and environmentally toxic, which raises concerns regarding its widespread use. As a result, we explored new synthetic substances as alternative strategies for controlling Biomphalaria glabrata. We evaluated the molluscicidal activity of 2-(1H-py-razol-1-yl)-1,3,4-thiadiazole and 2-(4,5-dihydro-1H-pyrazol-1-yl)-1,3,4-thiadiazole derivatives against B. glabrata snails and embryos, as well as Schistosoma cercariae (infective larvae). Methods: Adult and young snails were added to 24-well plates containing 20 synthetic compounds from the PDAN series for initial screening over 96 h at a concentration of 100 ppm. Water and NCL (2 ppm) were used as the negative and positive controls, respectively. Active compounds in the adult B. glabrata assay were selected for the tests vs. embryos and cercariae. Results: In the initial screen, only PDAN 52 (63 \u00b1 4%) and 79 (12 \u00b1 3%) showed molluscicidal activity at a concentration of 100 ppm up to 48 h. Consequently, we selected only PDAN 52. The LC50 value found in the tests on embryos after 24 h of treatment was 20 \u00b1 2 ppm and, after 48 h, it was 4 \u00b1 0.5 ppm. Against cercariae, we measured an LC50 value of 68 \u00b1 5 ppm after 4 h of treatment. PDAN 52 did not induce marked toxicity against a second mollusk, Physella acuta, after 48 h of exposure. Conclusions: We highlight the promising molluscicidal activity of PDAN 52 against different developmental stages of the mollusk, B. glabrata, as well the infective larvae of Schistosoma mansoni.<\/jats:p>","DOI":"10.3390\/ph18030429","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T12:03:06Z","timestamp":1742299386000},"page":"429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molluscicidal and Schistosomicidal Activities of 2-(1H-Pyrazol-1-yl)-1,3,4-thiadiazole Derivatives"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0330-992X","authenticated-orcid":false,"given":"Leonardo","family":"da Silva Rangel","sequence":"first","affiliation":[{"name":"Laboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Tadeu Gomes","family":"Gonzaga","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, West Zone Campus, State University of Rio de Janeiro (UERJ), Rio de Janeiro 20550-013, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cl\u00e1udia Rodrigues","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia Lindmar","family":"von Ranke","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Modeling and QSAR (Mod Mol QSAR), Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Rangel","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Modeling and QSAR (Mod Mol QSAR), Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-4608","authenticated-orcid":false,"given":"Jos\u00e9 Augusto Albuquerque dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0146-2218","authenticated-orcid":false,"given":"Nubia","family":"Boechat","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Synthesis-LASFAR-Farmanguinhos, Fiocruz 21041-250, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyla Nunes Farias","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"},{"name":"Postgraduate Program in Plant Biotechnology and Bioprocesses, Center of Health Sciences, Federal University of Rio de Janeiro, University City, Carlos Chagas Filho Avenue 373, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Pegas","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"},{"name":"Postgraduate Program in Plant Biotechnology and Bioprocesses, Center of Health Sciences, Federal University of Rio de Janeiro, University City, Carlos Chagas Filho Avenue 373, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-834X","authenticated-orcid":false,"given":"Robson Xavier","family":"Faria","sequence":"additional","affiliation":[{"name":"Laboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.curtheres.2019.06.001","article-title":"Schistosomiasis: Life Cycle, Diagnosis, and Control","volume":"91","author":"Nelwan","year":"2019","journal-title":"Curr. Ther. Res."},{"key":"ref_2","unstructured":"World Heath Organization (WHO) (2023, June 22). Schistosomiasis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/schistosomiasis\/."},{"key":"ref_3","unstructured":"Brasil, Minist\u00e9rio da Sa\u00fade, Secretaria de Vigil\u00e2ncia em Sa\u00fade e Ambiente, Departamento de Doen\u00e7as Transmiss\u00edveis (2024). Vigil\u00e2ncia da Esquistossomose Mansoni: Diretrizes T\u00e9cnicas [Recurso Eletr\u00f4nico]."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zacharia, A., Mushi, V., and Makene, T. (2020). A systematic review and meta-analysis on the rate of human schistosomiasis reinfection. PLoS ONE, 15.","DOI":"10.1101\/2020.07.18.20156703"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1080\/20477724.2022.2145070","article-title":"Praziquantel efficacy, urinary and intestinal schistosomiasis reinfection\u2014A systematic review","volume":"117","author":"Aboagye","year":"2022","journal-title":"Pathog. Glob. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e20190171","DOI":"10.1590\/0037-8682-0171-2019","article-title":"Prevalence of Infection of Biomphalaria glabrata by Schistosoma mansoni and the risk of urban Schistosomiasis mansoni in Salvador, Bahia, Brazil","volume":"52","author":"Zanardi","year":"2019","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40249-016-0153-6","article-title":"Critical analysis of molluscicide application in schistosomiasis control programs in Brazil","volume":"5","author":"Coelho","year":"2016","journal-title":"Infect. Dis. Poverty"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jglr.2019.11.007","article-title":"Acute toxicity of the lampricides TFM and niclosamide: Effects on a vascular plant and a chironomid species","volume":"46","author":"Leak","year":"2020","journal-title":"J. Great Lakes Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115081","DOI":"10.1016\/j.ecoenv.2023.115081","article-title":"Niclosamide exposure disrupts antioxidant defense, histology, and the liver and gut transcriptome of Chinese soft-shelled turtle (Pelodiscus sinensis)","volume":"260","author":"Xiang","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gonzaga, D.T.G., Oliveira, F.H., von Ranke, N.L., Pinho, G.Q., Salles, J.P., Bello, M.L., Rodrigues, C.R., Castro, H.C., de Souza, H.V.C.M., and Reis, C.R.C. (2019). Synthesis, Biological Evaluation, and Molecular Modeling Studies of New Thiadiazole Derivatives as Potent P2X7 Receptor Inhibitors. Front. Chem., 7.","DOI":"10.3389\/fchem.2019.00261"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1002\/mabi.201200017","article-title":"Poly(2-ethyl-2-oxazoline) as alternative for the stealth polymer poly(ethylene glycol): Comparison of in vitro cytotoxicity and hemocompatibility","volume":"12","author":"Bauer","year":"2012","journal-title":"Macromol. Biosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1590\/S0074-02762004000900003","article-title":"Epidemiological and control aspects of schistosomiasis in Brazilian endemic areas","volume":"99","author":"Coura","year":"2004","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1186\/s13071-015-1144-3","article-title":"Modelling control of Schistosoma haematobium infection: Predictions of the long-term impact of mass drug administration in Africa","volume":"8","author":"Gurarie","year":"2015","journal-title":"Parasites Vectors"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.ejmech.2008.09.006","article-title":"Synthesis and molluscicidal activity of some new thiophene, thiadiazole and pyrazole derivatives","volume":"44","author":"Fadda","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.ejmech.2010.01.030","article-title":"Synthesis of 3-((2,4-dichlorophenoxy)methyl)-1,2,4-triazolo(thiadiazoles and thiadiazines) as anti-inflammatory and molluscicidal agents","volume":"45","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.1016\/j.ejmech.2010.07.043","article-title":"Synthesis and molluscicidal evaluation of some new pyrazole, isoxazole, pyridine, pyrimidine, 1,4-thiazine and 1,3,4-thiadiazine derivatives incorporating benzofuran moiety","volume":"45","author":"Swellem","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/ardp.200600057","article-title":"Synthesis and Molluscicidal Activity of New Cinnoline and Pyrano [2,3-c]pyrazole Derivatives","volume":"339","author":"Abdelrazek","year":"2006","journal-title":"Arch. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/ardp.200500259","article-title":"Synthesis and Molluscicidal Activity of Some 1,3,4-Triaryl-5-chloropyrazole, Pyrano[2,3-c]pyrazole, Pyrazolylphthalazine and Pyrano[2,3-d]thiazole Derivatives","volume":"339","author":"Abdelrazek","year":"2006","journal-title":"Arch. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Casertano, M., Imperatore, C., Luciano, P., Aiello, A., Putra, M.Y., Gimmelli, R., Ruberti, G., and Menna, M. (2019). Chemical Investigation of the Indonesian Tunicate Polycarpa aurata and Evaluation of the Effects Against Schistosoma mansoni of the Novel Alkaloids Polyaurines A and B. Mar. Drugs, 17.","DOI":"10.3390\/md17050278"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40249-015-0071-z","article-title":"High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis","volume":"4","author":"Li","year":"2015","journal-title":"Infect. Dis. Poverty"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ferraro, F., Corvo, I., Bergalli, L., Ilarraz, A., Cabrera, M., Gil, J., Susuki, B.M., Caffrey, C.R., Timson, D.J., and Robert, X. (2020). Novel and selective inactivators of Triosephosphate isomerase with anti-trematode activity. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-59460-y"},{"key":"ref_22","unstructured":"EPA (2024, June 11). Prevention, Pesticides and Toxic Substances. United States Environmental Protection Agency, Available online: https:\/\/www3.epa.gov\/pesticides\/chem_search\/reg_actions\/reregistration\/fs_PC-077401_1-Nov-99.pdf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"142","DOI":"10.4269\/ajtmh.1979.28.142","article-title":"Cost of snail control","volume":"28","author":"Jobin","year":"1979","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e20210714","DOI":"10.1590\/0103-8478cr20210714","article-title":"Biological control of Biomphalaria, the intermediate host of Schistosoma spp.: A systematic review","volume":"53","author":"Friani","year":"2023","journal-title":"Cienc. Rural"},{"key":"ref_25","unstructured":"Pharmacompass (2025, February 07). Available online: https:\/\/www.pharmacompass.com\/price\/niclosamide."},{"key":"ref_26","unstructured":"Sigma Aldrich (2025, February 07). Available online: https:\/\/www.sigmaaldrich.com\/BR\/pt\/search\/niclodamide?dym=niclosamide&focus=products&page=1&perpage=30&sort=relevance&term=Niclodamide&type=product."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.scitotenv.2016.08.002","article-title":"Ecotoxicological water assessment of an estuarine river from the Brazilian Northeast, potentially affected by industrial wastewater discharge","volume":"572","author":"Gurgel","year":"2016","journal-title":"Sci. Total Environ."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ijpe.2006.11.029","article-title":"Confirmation of a measurement model for green supply chain management practices implementation","volume":"111","author":"Zhu","year":"2008","journal-title":"Int. J. Prod. Econ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100274","DOI":"10.1016\/j.dwt.2024.100274","article-title":"Persistent pesticides: Accumulation, health risk assessment, management and remediation: An overview","volume":"317","author":"Ansari","year":"2024","journal-title":"Desalin. Water Treat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106414","DOI":"10.1016\/j.actatropica.2022.106414","article-title":"Molluskicidal activity of 3-aryl-2-hydroxy-1,4-naphthoquinones against Biomphalaria glabrata","volume":"231","author":"Martins","year":"2022","journal-title":"Acta Trop."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1158\/1078-0432.CCR-13-3296","article-title":"Niclosamide Inhibits Androgen Receptor Variants Expression and Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer","volume":"20","author":"Liu","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s10637-018-0653-2","article-title":"Current status of androgen receptor-splice variant 7 inhibitor niclosamide in castrate-resistant prostate-cancer","volume":"36","author":"Sobhani","year":"2018","journal-title":"Investig. New Drugs"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Parikh, M., Liu, C., Wu, C.Y., Evans, C.P., Dall\u2019Era, M., Robles, D., Lara, P.N., Agarwal, N., Gao, A.C., and Pan, C.X. (2021). Phase Ib trial of reformulated niclosamide with abiraterone\/prednisone in men with castration-resistant prostate cancer. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-85969-x"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3673197","DOI":"10.1155\/2017\/3673197","article-title":"A New Technique Using Low Volumes: A New Technique to Assess the Molluscicidal Activity Using Low Volumes","volume":"2017","author":"Santos","year":"2017","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1590\/0001-3765202020200715","article-title":"Molluscicidal activity of Persea americana Mill. (Lauraceae) stem bark ethanolic extract against the snail Biomphalaria glabrata (Say, 1818): A novel plant-derived molluscicide?","volume":"92","author":"Silva","year":"2020","journal-title":"Ann. Braz. Acad. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e180489","DOI":"10.1590\/0074-02760180489","article-title":"Nanoemulsion containing essential oil from Xylopia ochrantha Mart. produces molluscicidal effects against different species of Biomphalaria (Schistosoma hosts)","volume":"114","author":"Rangel","year":"2019","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_37","unstructured":"ANVISA, and National Health Surveillance Agency (2013). Guide for Conducting Nonclinical Toxicology and Pharmacological Safety Studies Necessary for the Development of Medicine Safety and Efficacy Assessment Management, Version 2."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/3\/429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:56:10Z","timestamp":1760028970000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/3\/429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ph18030429"],"URL":"https:\/\/doi.org\/10.3390\/ph18030429","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]}}}