{"doi":"10.1093/jac/dkaa247","title":"Efficacy, metabolism and pharmacokinetics of Ro 15-5458, a forgotten schistosomicidal 9-acridanone hydrazone","abstract":"BACKGROUND: Treatment of schistosomiasis, a neglected disease, relies on just one partially effective drug, praziquantel. We revisited the 9-acridanone hydrazone, Ro 15-5458, a largely forgotten antischistosomal lead compound. METHODS: Ro 15-5458 was evaluated in juvenile and adult Schistosoma mansoni-infected mice. We studied dose-response, hepatic shift and stage specificity. The metabolic stability of Ro 15-5458 was measured in the presence of human and mouse liver microsomes, and human hepatocytes; the latter also served to identify metabolites. Pharmacokinetic parameters were measured in naive mice. The efficacy of Ro 15-5458 was also assessed in S. haematobium-infected hamsters and S. japonicum-infected mice. RESULTS: Ro 15-5458 had single-dose ED50 values of 15 and 5.3 mg/kg in mice harbouring juvenile and adult S. mansoni infections, respectively. An ED50 value of 17 mg/kg was measured in S. haematobium-infected hamsters; however, the compound was inactive at up to 100 mg/kg in S. japonicum-infected mice. The drug-induced hepatic shift occurred between 48 and 66 h post treatment. A single oral dose of 50 mg/kg of Ro 15-5458 had high activity against all tested S. mansoni stages (1-, 7-, 14-, 21- and 49-day-old). In vitro, human hepatocytes produced N-desethyl and glucuronide metabolites; otherwise Ro 15-5458 was metabolically stable in the presence of microsomes or whole hepatocytes. The maximum plasma concentration was approximately 8.13 μg/mL 3 h after a 50 mg/kg oral dose and the half-life was approximately 4.9 h. CONCLUSIONS: Ro 15-5458 has high activity against S. mansoni and S. haematobium, yet lacks activity against S. japonicum, which is striking. This will require further investigation, as a broad-spectrum antischistosomal drug is desirable.","journal":"Journal of Antimicrobial Chemotherapy","year":2020,"id":110520,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":526463,"name":"Cécile Häberli","orcid":null,"position":1,"is_corresponding":false},{"id":225261,"name":"Dionicio Siegel","orcid":"0000-0003-4674-9554","position":2,"is_corresponding":false},{"id":323862,"name":"Jianbo Huang","orcid":"0000-0002-0265-7917","position":3,"is_corresponding":false},{"id":526464,"name":"Seth Vigneron","orcid":null,"position":4,"is_corresponding":false},{"id":526465,"name":"Anh P. Ta","orcid":null,"position":5,"is_corresponding":false},{"id":379454,"name":"Danielle Skinner","orcid":"0000-0002-5346-1308","position":6,"is_corresponding":false},{"id":379453,"name":"Nelly El‐Sakkary","orcid":"0000-0003-3357-0424","position":7,"is_corresponding":false},{"id":330629,"name":"Jeremiah D. Momper","orcid":"0000-0002-3154-6685","position":8,"is_corresponding":false},{"id":335997,"name":"Jon A. Gangoiti","orcid":null,"position":9,"is_corresponding":false},{"id":431732,"name":"Yuxiang Dong","orcid":"0000-0003-1412-3178","position":10,"is_corresponding":false},{"id":431734,"name":"Jonathan L. Vennerstrom","orcid":"0000-0003-0075-2336","position":11,"is_corresponding":false},{"id":471524,"name":"Susan A. Charman","orcid":"0000-0003-1753-8213","position":12,"is_corresponding":false},{"id":241386,"name":"Conor R. Caffrey","orcid":"0000-0003-3048-8572","position":13,"is_corresponding":false},{"id":525681,"name":"Jennifer Keiser","orcid":"0000-0003-0290-3521","position":14,"is_corresponding":false},{"id":525680,"name":"Alexandra Probst","orcid":"0000-0001-7946-522X","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-18T23:12:57.988348Z","pmid":"32617557","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}