{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:11:24Z","timestamp":1791825084821,"version":"4.3.4"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa Do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["201622488-3"],"award-info":[{"award-number":["201622488-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Human helminthiasis affects approximately one in five people in the world and disproportionally affects the poorest and most deprived communities. Human angiostrongyliasis, caused by nematode <jats:italic>Angiostrongylus cantonensis<\/jats:italic>, is a neglected emerging disease with escalating importance worldwide. Chemotherapy is the main control method for helminthiasis, but the therapeutic arsenal is limited. This study aimed to evaluate the antiparasitic and molecular properties of the major available anthelmintic drugs against <jats:italic>A. cantonensis in vitro<\/jats:italic>. The first-stage larvae (L1), isolated from feces of an <jats:italic>A. cantonensis<\/jats:italic>-infected rat, were exposed to a set of 12 anthelmintic drugs <jats:italic>in vitro<\/jats:italic>. The larvae were monitored, and the concentration- and time-dependent viability alterations were determined. From 12 anthelmintic drugs, six (ivermectin, salamectin, moxidectin, pyrantel pamoate, albendazole and levamisole) were identified to affect the viability of <jats:italic>A. cantonensis<\/jats:italic>. The macrocyclic lactones (ivermectin, salamectin, moxidectin) and the imidazothiazole levamisole, were the most effective drugs, with IC<jats:sub>50<\/jats:sub> ranging from 2.2 to 2.9\u00a0\u00b5M and a rapid onset of action. Albendazole, the most widely used anthelmintic in humans, had a slower onset of action, but an IC<jats:sub>50<\/jats:sub> of 11.3\u00a0\u00b5M was achieved within 24\u00a0h. Molecular properties studies suggest that a less lipophilic character and low molecular weight could be favorable for the biological activity of the non-macrocyclic molecules. Collectively, our study revealed that macrocyclic lactones, levamisole, pyrantel pamoate, and albendazole are important anthelmintic agents against <jats:italic>A. cantonensis<\/jats:italic>. The results of this <jats:italic>in vitro<\/jats:italic> study also suggest that <jats:italic>A. cantonensis<\/jats:italic> L1 may be a particularly sensitive and useful model for anthelmintic studies.<\/jats:p>","DOI":"10.3389\/fphar.2022.901459","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T04:35:53Z","timestamp":1655786153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Susceptibility of Angiostrongylus cantonensis Larvae to Anthelmintic Drugs"],"prefix":"10.3389","volume":"13","author":[{"given":"Daniel B.","family":"Roquini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel L.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo L. G.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano D.","family":"Andricopulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polrat","family":"Wilairatana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josu\u00e9","family":"De Moraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1021\/acsinfecdis.0c00435","article-title":"Characterization of Moxidectin against Strongyloides Ratti: In Vitro and In Vivo Activity and Pharmacokinetics in the Rat Model","volume":"7","author":"Buchter","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.ijpddr.2021.12.001","article-title":"Advances in Our Understanding of Nematode Ion Channels as Potential Anthelmintic Targets","volume":"18","author":"Choudhary","year":"2022","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1021\/acschemneuro.7b00335","article-title":"Angiostrongylus Cantonensis: Agent of a Sometimes Fatal Globally Emerging Infectious Disease (Rat Lungworm Disease)","volume":"8","author":"Cowie","year":"2017","journal-title":"Acs. Chem. Neurosci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e05150","DOI":"10.1016\/j.heliyon.2020.e05150","article-title":"First Record of Natural Infection by Angiostrongylus Cantonensis (Nematoda: Metastrongyloidea) in Belocaulus Willibaldoi and Rattus norvegicus in an Urban Area of S\u00e3o Paulo City, SP, Brazil","volume":"6","author":"da Mota","year":"2020","journal-title":"Heliyon"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e01372","DOI":"10.1128\/AAC.01372-20","article-title":"Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma Mansoni Infection","volume":"64","author":"de Brito","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.pt.2020.04.005","article-title":"FDA-approved Antiparasitic Drugs in the 21st Century: A Success for Helminthiasis?","volume":"36","author":"de Moraes","year":"2020","journal-title":"Trends. Parasitol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"9680986","DOI":"10.3389\/fpubh.2021.680986","article-title":"Trade and Deforestation Predict Rat Lungworm Disease, an Invasive-Driven Zoonosis, at Global and Regional Scales","volume":"9","author":"de Wit","year":"2021","journal-title":"Front. Public Health"},{"key":"B8","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.ijid.2020.01.012","article-title":"Eosinophilic Meningitis Due to Angiostrongylus Cantonensis in Europe","volume":"93","author":"Federspiel","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"00135","DOI":"10.1016\/j.drudis.2022.04.004","article-title":"Approaches to Advance Drug Discovery for Neglected Tropical Diseases","volume":"22","author":"Ferreira","year":"2022","journal-title":"Drug Discov. Today"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpara.2009.11.001","article-title":"Unresolved Issues in Anthelmintic Pharmacology for Helminthiases of Humans","volume":"40","author":"Geary","year":"2010","journal-title":"Int. J. Parasitol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3390\/ph14020153","article-title":"Pharyngeal Pumping and Tissue-specific Transgenic P-Glycoprotein Expression Influence Macrocyclic Lactone Susceptibility in Caenorhabditis elegans","volume":"14","author":"Gerhard","year":"2021","journal-title":"Pharm. (Basel)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e01722","DOI":"10.1128\/AAC.01722-18","article-title":"In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing","volume":"63","author":"Guerra","year":"2019","journal-title":"Antimicrob. Agents. Chemother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpddr.2022.04.002","article-title":"In Vivo efficacy of Pyrantel Pamoate as a Post-exposure Prophylactic for Rat Lungworm (Angiostrongylus Cantonensis)","volume":"19","author":"Jacob","year":"2022","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"B14","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1017\/S0031182020001146","article-title":"In Vitro efficacy of Anthelmintics on Angiostrongylus Cantonensis L3 Larvae","volume":"148","author":"Jacob","year":"2021","journal-title":"Parasitology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1021\/acsinfecdis.0c00719","article-title":"Evaluation of Commercially Available Anthelminthics in Laboratory Models of Human Intestinal Nematode Infections","volume":"7","author":"Keiser","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.ebiom.2019.04.029","article-title":"Phenotypic Screening of Nonsteroidal Anti-inflammatory Drugs Identified Mefenamic Acid as a Drug for the Treatment of Schistosomiasisflammatory Drugs Identified Mefenamic Acid as a Drug for the Treatment of Schistosomiasis","volume":"43","author":"Lago","year":"2019","journal-title":"EBioMedicine"},{"key":"B17","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1080\/17425247.2022.2051477","article-title":"Recent Trends in Praziquantel Nanoformulations for Helminthiasis Treatment","volume":"19","author":"Mengarda","year":"2022","journal-title":"Expert Opin. Drug Deliv."},{"key":"B18","doi-asserted-by":"publisher","first-page":"23437","DOI":"10.1038\/s41598-021-02792-0","article-title":"Pyrazoline Derivatives as Promising Novel Antischistosomal Agents","volume":"11","author":"Morais","year":"2021","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"j4307","DOI":"10.1136\/bmj.j4307","article-title":"Efficacy of Recommended Drugs against Soil Transmitted Helminths: Systematic Review and Network Meta-Analysis","volume":"358","author":"Moser","year":"2017","journal-title":"BMJ"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e0004698","DOI":"10.1371\/journal.pntd.0004698","article-title":"An In Vitro\/In Vivo Model to Analyze the Effects of Flubendazole Exposure on Adult Female Brugia malayi","volume":"10","author":"O'Neill","year":"2016","journal-title":"PLoS. Negl. Trop. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/nrd1824","article-title":"Opportunities and Challenges in Antiparasitic Drug Discovery","volume":"4","author":"Pink","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"B22","doi-asserted-by":"publisher","first-page":"686","DOI":"10.3390\/ph14070686","article-title":"Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma Mansoni","volume":"14","author":"Porto","year":"2021","journal-title":"Pharm. (Basel)"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e01208","DOI":"10.1128\/AAC.01208-19","article-title":"Promethazine Exhibits Antiparasitic Properties In Vitro and Reduces Worm Burden, Egg Production, Hepato-, and Splenomegaly in a Schistosomiasis Animal Model","volume":"63","author":"Roquini","year":"2019","journal-title":"Antimicrob. Agents. Chemother."},{"key":"B24","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/0014-4894(84)90074-2","article-title":"Angiostrongylus Cantonensis: Paralysis Due to Avermectin B1a and Ivermectin","volume":"57","author":"Terada","year":"1984","journal-title":"Exp. Parasitol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1254\/jjp.32.633","article-title":"Studies on Chemotherapy of Parasitic Helminths (VII). Effects of Various Cholinergic Agents on the Motility of Angiostrongylus Cantonensis","volume":"32","author":"Terada","year":"1982","journal-title":"Jpn. J. Pharmacol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1007\/BF01990115","article-title":"Studies on Chemotherapy of Parasitic Helminths (XVIII). Mechanism of Spastically Paralyzing Action of Pyrantel in Angiostrongylus Cantonensis","volume":"39","author":"Terada","year":"1983","journal-title":"Experientia"},{"key":"B27","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/BF00928748","article-title":"Effects of Diethylcarbamazine on the Motility of Angiostrongylus Cantonensis and Dirofilaria Immitis","volume":"72","author":"Terada","year":"1986","journal-title":"Z. Parasitenkd."},{"key":"B28","first-page":"365","article-title":"Studies on Chemotherapy of Parasitic Helminths (XXVI). Comparative In Vitro Effects if Various Anthelmintics on the Motility of Angiostrongylus Costaricensis and A. Cantonensis","volume":"35","author":"Terada","year":"1986","journal-title":"Jap. J. Parasit."},{"key":"B29","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.pt.2020.11.008","article-title":"Complementary Approaches with Free-Living and Parasitic Nematodes to Understanding Anthelmintic Resistance","volume":"37","author":"Wit","year":"2021","journal-title":"Trends Parasitol."},{"key":"B30","unstructured":"Ending the Neglect to Attain the Sustainable Development Goals: a Road Map for Neglected Tropical Diseases 2021\u20132030"},{"key":"B31","unstructured":"Model List of Essential Medicines \u2013 22nd List"},{"key":"B32","unstructured":"Soil-transmitted Helminth Infections2022"},{"key":"B33","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/s13071-020-04140-z","article-title":"H1-antihistamines as Antischistosomal Drugs: In Vitro and In Vivo Studies","volume":"13","author":"Xavier","year":"2020","journal-title":"Parasit. Vectors"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.901459\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T04:35:57Z","timestamp":1655786157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.901459\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,21]]},"references-count":33,"alternative-id":["10.3389\/fphar.2022.901459"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.901459","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,21]]},"article-number":"901459"}}