Phenotypic screening of nonsteroidal anti-inflammatory drugs identified mefenamic acid as a drug for the treatment of schistosomiasis
| Autor: | Talita Gonçalves Aires de Queiroz, Pedro Luiz Silva Pinto, Josué de Moraes, Leonardo L. G. Ferreira, Vinícius C. Rodrigues, Jefferson Almeida Rocha, Susana F. Mazloum, Eloi M Lago, Marcos P. Silva, Adriano D. Andricopulo, Paulo U. Carnaúba |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Drug Research paper Mefenamic acid media_common.quotation_subject Drug Evaluation Preclinical Schistosomiasis Pharmacology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mefenamic Acid Mice Schistosomicides 0302 clinical medicine Diclofenac Tolfenamic acid Parasitic Sensitivity Tests In vivo medicine Animals Humans media_common CRISTALOGRAFIA FÍSICA biology Dose-Response Relationship Drug business.industry Anti-Inflammatory Agents Non-Steroidal Drug Repositioning General Medicine Schistosoma mansoni biology.organism_classification medicine.disease Meclofenamic acid Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Schistosoma Female business medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 2352-3964 |
| Popis: | Background Treatment and control of schistosomiasis, one of the most insidious and serious parasitic diseases, depend almost entirely on a single drug, praziquantel. Since the funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, 73 nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in medical and veterinary fields were evaluated for their anti-schistosomal properties. Methods The efficacy of NSAIDs was first tested against adult Schistosoma mansoni ex vivo using phenotypic screening strategy, effective drugs were further tested in a murine model of schistosomiasis. The disease parameters measured were worm and egg burden, hepato- and splenomegaly. Findings From 73 NSAIDs, five (mefenamic acid, tolfenamic acid, meclofenamic acid, celecoxib, and diclofenac) were identified to effectively kill schistosomes. These results were further supported by scanning electron microscopy analysis. In addition, the octanol-water partition coefficient, both for neutral and ionized species, revealed to be a critical property for the ex vivo activity profile. Compounds were then tested in vivo using both patent and a prepatent S. mansoni infection in a mouse model. The most effective NSAID was mefenamic acid, which highly reduced worm burden, egg production, and hepato- and splenomegaly. Interpretation The treatment regimen used in this study is within the range for which mefenamic acid has been used in clinical practice, thus, it is demonstrated the capacity of mefenamic acid to act as a potent anti-schistosomal agent suitable for clinical repurposing in the treatment of schistosomiasis. |
| Databáze: | OpenAIRE |
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