title: Evaluation of the anti-Schistosoma mansoni activity of thiosemicarbazones and thiazoles.
abstract: 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.
authors.affiliation: Department of Pharmacy, Federal University of Pernambuco, Recife, PE, Brazil.
authors.forename: Edna de Farias
authors.initials: Ede F
authors.lastname: Santiago
authors.forename: Sheilla Andrade
authors.initials: SA
authors.lastname: de Oliveira
authors.forename: Gevânio Bezerra
authors.initials: GB
authors.lastname: de Oliveira Filho
authors.forename: Diogo Rodrigo Magalhaes
authors.initials: DR
authors.lastname: Moreira
authors.forename: Paulo André Teixeira
authors.initials: PA
authors.lastname: Gomes
authors.forename: Anekécia Lauro
authors.initials: AL
authors.lastname: da Silva
authors.forename: Andréia Ferreira
authors.initials: AF
authors.lastname: de Barros
authors.forename: Aline Caroline
authors.initials: AC
authors.lastname: da Silva
authors.forename: Thiago André Ramos
authors.initials: TA
authors.lastname: Dos Santos
authors.forename: Valéria Rêgo Alves
authors.initials: VR
authors.lastname: Pereira
authors.forename: Gabriel Gazzoni Araújo
authors.initials: GG
authors.lastname: Gonçalves
authors.forename: Fábio André
authors.initials: FA
authors.lastname: Brayner
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Alves
authors.forename: Almir Gonçalves
authors.initials: AG
authors.lastname: Wanderley
authors.forename: Ana Cristina Lima
authors.initials: AC
authors.lastname: Leite
mesh_terms: D000818:Animals; D006801:Humans; D008855:Microscopy, Electron, Scanning; D012550:Schistosoma mansoni / Q000187:drug effects*; D012556:Schistosomicides / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000494:pharmacology*
chemical_list: D012556:Schistosomicides; D013844:Thiazoles; D013882:Thiosemicarbazones