Evaluation of the anti-Schistosoma mansoni activity of thiosemicarbazones and thiazoles
| Autor: | Ana Cristina Lima Leite, Luiz Carlos Alves, Thiago André Ramos dos Santos, Sheilla Andrade de Oliveira, Gevânio Bezerra de Oliveira Filho, Edna de Farias Santiago, Gabriel Gazzoni Araújo Gonçalves, Anekécia Lauro Da Silva, Fábio André Brayner, Andréia Ferreira de Barros, Paulo André Teixeira de Moraes Gomes, Diogo Rodrigo Magalhães Moreira, Aline Caroline da Silva, Valéria Rêgo Alves Pereira, Almir Gonçalves Wanderley |
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| Rok vydání: | 2013 |
| Předmět: |
Drug
Thiosemicarbazones media_common.quotation_subject Schistosomicides Schistosomiasis Pharmacology chemistry.chemical_compound parasitic diseases medicine Animals Humans Pharmacology (medical) Experimental Therapeutics Thiazole Schistosoma media_common biology Viral tegument Schistosoma mansoni biology.organism_classification medicine.disease Praziquantel Thiazoles Infectious Diseases chemistry Immunology Microscopy Electron Scanning medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 58(1) |
| ISSN: | 1098-6596 |
| Popis: | Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma and affects over 207 million people. Chemotherapy is the only immediate recourse for minimizing the prevalence of this disease and involves predominately the administration of a single drug, praziquantel (PZQ). Although PZQ has proven efficacy, there is a recognized need to develop new drugs as schistosomicides since studies have shown that repeated use of this drug in areas of endemicity may cause a temporary reduction in susceptibility in isolates of Schistosoma mansoni . Hydrazones, thiosemicarbazones, phthalimides, and thiazoles are thus regarded as privileged structures used for a broad spectrum of activities and are potential candidates for sources of new drug prototypes. The present study determined the in vitro schistosomicidal activity of 10 molecules containing these structures. During the assays, parameters such motility and mortality, oviposition, morphological changes in the tegument, cytotoxicity, and immunomodulatory activity caused by these compounds were evaluated. The results showed that compounds formed of thiazole and phthalimide led to higher mortality of worms, with a significant decline in motility, inhibition of pairing and oviposition, and a mortality rate of 100% starting from 144 h of exposure. These compounds also stimulated the production of nitric oxide and tumor necrosis factor alpha (TNF-α), thereby demonstrating the presence of immunomodulatory activity. The phthalyl thiazole LpQM-45 caused significant ultrastructural alterations, with destruction of the tegument in both male and female worms. According to the present study, phthalyl thiazole compounds possess antischistosomal activities and should form the basis for future experimental and clinical trials. |
| Databáze: | OpenAIRE |
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