Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

Abstract

f 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-␣), 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.

In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes

“…Generally, if a drug induces tegumental alterations, the onset and precise pattern of these alterations depend on the particular drug and the treatment regimen used (44) . The characteristic features of tegumental damage observed in this study, including destruction of the tegument and erosion and loss of spines, were consistent with those previously described in the literature following in vitro exposure to different antischistosomal agents such as hypericin (45) , allicin (46) , nerolidol (47) , phthalyl thiazole (LpQM-45) (48) , β-lapachone (49) , and DNK (32) . Hence, reductions in worms may be attributed to the tegumental damage observed.…”

Synthesis and structure–activity relationship study of a new series of antiparasitic aryloxyl thiosemicarbazones inhibiting Trypanosoma cruzi cruzain

“…BALB/c mouse, housed in the Centro de Pesquisas Aggeu Magalhaes (Recife, Brazil), were used to collect splenocytes accordingly to a previously reported protocol [48]. T.…”

Atividade in Vitro De Compostos Derivados De Tiazóis Sobre Melanomamurino

“…Neste trabalho foram utilizados esplenócitos, obtidos de camundongos BALB/c machos (SANTIAGO et al, 2014). Os esplenócitos foram mantidos em meio RPMI 1640 suplementado com 10% de soro fetal bovino (SFB).…”