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1. Introduction
Schistosomiasis is the second most significant parasitic disease in the world after malaria in terms of socioeconomic and public health importance. It is estimated that 207 million people are infected in 74 countries throughout Latin America, Africa, and Asia and more than 779 million people are at risk of infection, with mortality estimated at up to 280,000 deaths annually in sub-Saharan Africa alone [1–3]. Estimates of the global burden of schistosomiasis range from 1.7 to 4.5 million disability-adjusted life years (DALYs) lost [4–6] or even higher [7].
Chemotherapy is currently the main strategy in use for schistosomiasis control. Praziquantel (2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexa-hydro-4H-pyrazino{2,1-a}isoquinoline-4-one) is the drug of choice for the treatment of schistosomiasis because of its efficacy against all schistosome species [8, 9]. The control of Asian schistosomiasis has relied on large-scale chemotherapy using the praziquantel [10]. However, mass treatment does not prevent reinfection [11]. Data assembled over the past five years suggest that schistosomiasis is reemerging in parts of China [12]. Furthermore, despite the fact that there is not yet clear-cut evidence for the existence of praziquantel-resistant schistosome strains, decreased susceptibility to the drug has been reported in several countries [11]. The reliance on one single antischistosomal drug is alarming and the scientific community has called for research and development of novel and inexpensive drugs against schistosomiasis [13, 14].
The imidazolidines are a broad class of bioactive pentagonal heterocyclic compounds with diverse biological activity [15]. The imidazolidine system has antifungal and antimicrobial properties [16], hypnotic [17], and hypoglycemic [18, 19] effects.
Niridazole, 1-(5-nitro-thiazol-2-yl)-imidazolidin-2-one, has been used over the past century for its schistosomicidal properties. The drug received considerable attention, probably because it was one of the early treatment options to be administered orally [20].
The schistosomicidal properties of imidazolidine derivatives have been demonstrated by in vitro studies with adult S. mansoni worms [21–25]. The 3-benzyl-5-(4-chloro-arylazo)-4thioxo-imidazolidin-2-one, also known as LPSF-PT05 (CAS Registry Number 197504-87-3) [26], used in this work was synthesized by the Laboratório de Planejamento e Síntese de Fármacos (LPSF) (UFPE) using diazonium ions formed from a phenylamine that acts as an electrophilic reagent and engages with the active hydrogen in position 5 of 3-benzyl-4thioxo-imidazolidine-2-one, yielding the arylazo imidazolidine [27].
Recently, Neves and collaborators [28] demonstrated the schistosomicidal activity in vitro of LPSF-PT05 with...