{"doi":"10.1101/2020.03.19.999664","title":"Orally Bioavailable Endochin-like Quinolone Carbonate Ester Prodrug Reduces <i>Toxoplasma gondii</i> Brain Cysts","abstract":"Abstract Toxoplasmosis is a potentially fatal infection for immunocompromised people and the developing fetus. Current medicines for toxoplasmosis have high rates of adverse effects that interfere with therapeutic and prophylactic regimens. Endochin-like quinolones (ELQs) are potent inhibitors of Toxoplasma gondii proliferation in vitro and in animal models of acute and latent infection. ELQ-316, in particular, was found to be effective orally against acute toxoplasmosis in mice and highly selective for the T. gondii cytochrome b over the human cytochrome b . Despite oral efficacy, the high crystallinity of ELQ-316 limits oral absorption, plasma concentrations and therapeutic potential. A carbonate ester prodrug of ELQ-316, ELQ-334, was created to decrease crystallinity and increase oral bioavailability, which resulted in a six-fold increase in both C max (maximum plasma concentration) and AUC (area under the curve) of ELQ-316. The increased bioavailability of ELQ-316, when administered as ELQ-334, resulted in greater efficacy than the equivalent dose of ELQ-316 against acute toxoplasmosis and had similar efficacy against latent toxoplasmosis compared to intraperitoneal administration of ELQ-316. Carbonate ester prodrugs are a successful strategy to overcome the limited oral bioavailability of ELQs for the treatment of toxoplasmosis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":129155,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"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":580379,"name":"Tracey L. Schultz","orcid":"0009-0008-3133-8756","position":1,"is_corresponding":false},{"id":467673,"name":"Alyssa J. Miller","orcid":"0000-0002-4069-1550","position":2,"is_corresponding":false},{"id":580380,"name":"Igor Bruzual","orcid":"0000-0003-4155-7596","position":3,"is_corresponding":false},{"id":382216,"name":"Sovitj Pou","orcid":null,"position":4,"is_corresponding":false},{"id":382217,"name":"Rolf W. Winter","orcid":null,"position":5,"is_corresponding":false},{"id":381170,"name":"Rozalia A. Dodean","orcid":"0000-0001-5002-4607","position":6,"is_corresponding":false},{"id":580381,"name":"Lev N. Zakharov","orcid":"0000-0002-8680-3474","position":7,"is_corresponding":false},{"id":317898,"name":"Aaron Nilsen","orcid":"0000-0002-3827-8222","position":8,"is_corresponding":false},{"id":381169,"name":"Michael K. Riscoe","orcid":"0000-0002-1343-5279","position":9,"is_corresponding":false},{"id":368848,"name":"Vern B. Carruthers","orcid":"0000-0001-6859-8895","position":10,"is_corresponding":false},{"id":352978,"name":"J. Stone Doggett","orcid":"0000-0002-6098-1520","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:45.920615Z","pmid":null,"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":[]}