ArticleAntimicrobial agents and chemotherapy2015
ELQ-300 prodrugs for enhanced delivery and single-dose cure of malaria.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- Article
- Identifying antimalarials that disrupt malaria parasite transmission when fed to the mosquito.International journal for parasitology · 2025Article
- Acridone Prodrugs with Enhanced Dual-Stage Antimalarial Efficacy.ACS medicinal chemistry letters · 2025Article
- Article
- Synthesis, Docking, and Biological Studies of Pyrazine Derivatives as Antimycobacterial Agents.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Article
- The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb AgainstPharmaceutics · 2024Article
- Chemoprevention of malaria with long-acting oral and injectable drugs: an updated target product profile.Malaria journal · 2024Review
- Incorporation of an Isohexide Subunit into the Endochin-like Quinolone Scaffold.Molecules (Basel, Switzerland) · 2024Article
- Mitochondrial CytochromeTropical medicine and infectious disease · 2024Review
- Antimalarial Dibenzannulated Medium-Ring Keto Lactams.ACS infectious diseases · 2023Article
- Unique Properties of Apicomplexan Mitochondria.Annual review of microbiology · 2023Review
- The evaluation of ADME and pharmacokinetic properties of decoquinate derivatives for the treatment of malaria.Frontiers in pharmacology · 2022Article
- Endochin-like quinolones (ELQs) and bumped kinase inhibitors (BKIs): Synergistic and additive effects of combined treatments against Neospora caninum infection in vitro and in vivo.International journal for parasitology. Drugs and drug resistance · 2021Article
- Assessment of the Activity of Decoquinate and Its Quinoline-Molecules (Basel, Switzerland) · 2021Article
- Treatment of Human Babesiosis: Then and Now.Pathogens (Basel, Switzerland) · 2021Review
- Effective Therapy Targeting CytochromeAntimicrobial agents and chemotherapy · 2021Article
- Aminoalkoxycarbonyloxymethyl Ether Prodrugs with a pH-Triggered Release Mechanism: A Case Study Improving the Solubility, Bioavailability, and Efficacy of Antimalarial 4(1Journal of medicinal chemistry · 2021Article
- Novel Antimalarial Tetrazoles and Amides Active against the Hemoglobin Degradation Pathway inJournal of medicinal chemistry · 2021Article
- Efforts Made to Eliminate Drug-Resistant Malaria and Its Challenges.BioMed research international · 2021Review
- Orally Bioavailable Endochin-Like Quinolone Carbonate Ester Prodrug Reduces Toxoplasma gondii Brain Cysts.Antimicrobial agents and chemotherapy · 2020Article
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Authors and funding
22 authors.
Funding
Abstract
ELQ-300 is a preclinical candidate that targets the liver and blood stages of Plasmodium falciparum, as well as the forms that are crucial to transmission of disease: gametocytes, zygotes, and ookinetes. A significant obstacle to the clinical development of ELQ-300 is related to its physicochemical properties. Its relatively poor aqueous solubility and high crystallinity limit absorption to the degree that only low blood concentrations can be achieved following oral dosing. While these low blood concentrations are sufficient for therapy, the levels are too low to establish an acceptable safety margin required by regulatory agencies for clinical development. One way to address the challenging physicochemical properties of ELQ-300 is through the development of prodrugs. Here, we profile ELQ-337, a bioreversible O-linked carbonate ester prodrug of the parent molecule. At the molar equivalent dose of 3 mg/kg of body weight, the delivery of ELQ-300 from ELQ-337 is enhanced by 3- to 4-fold, reaching a maximum concentration of drug in serum (C max) of 5.9 μM by 6 h after oral administration, and unlike ELQ-300 at any dose, ELQ-337 provides single-dose cures of patent malaria infections in mice at low-single-digit milligram per kilogram doses. Our findings show that the prodrug strategy represents a viable approach to overcome the physicochemical limitations of ELQ-300 to deliver the active drug to the bloodstream at concentrations sufficient for safety and toxicology studies, as well as achieving single-dose cures.
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