In Situ Preparation of Dehydrodieugenol-Loaded Silver Nanoparticles and their Antischistosomal Activity.

Schistosomiasis is a major neglected disease that imposes a substantial worldwide health burden, affecting approximately 250 million people globally. As praziquantel is the only available drug to treat schistosomiasis, there is a critical need to identify new anthelmintic compounds, particularly from natural sources. To enhance the activity of different natural products, one potential avenue involves its combination with silver nanoparticles (AgNP). Based on this approach, a one-step green method for the in situ preparation of dehydrodieugenol (DHDG) by oxidation coupling reaction using silver and natural eugenol is presented. AgNP formation was confirmed by UV-Vis spectroscopy due to the appearance of the surface plasmon resonance (SPR) band at 430 nm which is characteristic of silver nanoparticles. The nanoparticles were spherical with sizes in the range of 40 to 50 nm. Bioassays demonstrated that the silver nanoparticles loaded with DHDG exhibited significant anthelmintic activity against Schistosoma mansoni adult worms without toxicity to mammalian cells and an in vivo animal model (Caenorhabditis elegans), contributing to the development of new prototypes based on natural products for the treatment of schistosomiasis.

Targeting the Schistosoma mansoni nutritional mechanisms to design new antischistosomal compounds.

The chemical classes of semicarbazones, thiosemicarbazones, and hydrazones are present in various compounds, each demonstrating diverse biological activities. Extensive studies have revealed their potential as schistosomicidal agents. Thiosemicarbazones, in particular, have shown inhibitory effects on Schistosoma mansoni's cathepsin B1 enzyme (SmCB1), which plays a crucial role in hemoglobin degradation within the worm's gut and its nutrition processes. Consequently, SmCB1 has emerged as a promising target for novel schistosomiasis therapies. Moreover, chloroquinoline exhibits characteristics in its aromatic structure that hold promise for developing SmCB1 inhibitors, along with its interaction with hemoglobin's heme group, potentially synergizing against the parasite's gut. In this context, we report the synthesis of 22 hybrid analogs combining hydrazones and quinolines, evaluated against S. mansoni. Five of these hybrids demonstrated schistosomicidal activity in vitro, with GPQF-8Q10 being the most effective, causing worm mortality within 24 h at a concentration of 25 µM. GPQF-8Q8 proved to be the most promising in vivo, significantly reducing egg presence in feces (by 52.8%) and immature eggs in intestines (by 45.8%). These compounds exhibited low cytotoxicity in Vero cells and an in in vivo animal model (Caenorhabditis elegans), indicating a favorable selectivity index. This suggests their potential for the development of new schistosomiasis therapies. Further studies are needed to uncover specific target mechanisms, but these findings offer a promising starting point.

Licarin A, a neolignan isolated from Nectandra oppositifolia Nees & Mart. (Lauraceae), exhibited moderate preclinical efficacy against Schistosoma mansoni infection.

Schistosomiasis is a widespread human parasitic disease currently affecting over 200 million people, particularly in poor communities. Chemotherapy for schistosomiasis relies exclusively on praziquantel (PZQ). Previous studies have shown that licarin A (LIC-A), a dihydrobenzofuran neolignan, exhibited in vitro antiparasitic activity against Schistosoma mansoni adult worms. This study aimed to investigate the potential of LIC-A, isolated as main metabolite from leaves of Nectandra oppositifolia Nees & Mart. (Lauraceae), as an antischistosomal agent orally active in schistosomiasis animal model. PZQ was used as a reference compound. As result, LIC-A showed, at a single dose of 400 mg/kg, to be able to partially cure infected mice (worm burden reductions of ~50%). Parasite eggs, that are responsible for a variety of pathologies and transmission of schistosomiasis, were also moderately inhibited by LIC-A (egg burden reductions of ~50%-60%). Furthermore, it was observed that LIC-A achieved a slight reduction of hepatomegaly and splenomegaly. Collectively, although LIC-A was partially active when administered orally, these results give support for the antiparasitic potential LIC-A as lead compound for novel antischistosomal agent.

Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni Infection.

Praziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Schistosoma Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites. In this study, we evaluated the antiparasitic properties of diminazene against Schistosoma mansoniex vivo and in mice harboring either chronic or early S. mansoni infections. In vitro, we monitored phenotypic and tegumental changes as well as the effects of the drug on pairing and egg production. In mice infected with either adult (chronic infection) or immature (early infection) worms, diminazene was administered intraperitoneally (10 to 100 mg/kg of body weight) or by oral gavage (100 to 400 mg/kg), and we studied the influence of the drug on worm burden and egg production. Liver and spleen pathologies and serum aminotransferase levels were also analyzed. In vitro, 50% effective concentrations (EC50) and EC90 revealed that diminazene is able to kill both immature and adult parasites, and its effect was time and concentration dependent. In addition, confocal laser scanning microscopy showed morphological alterations in the teguments of schistosomes. In an animal model, the influence of the drug on worm burden, egg production, hepatomegaly, and splenomegaly depended on the dosing regimen applied and the route of administration. Diminazene also caused a significant reduction in aminotransferase levels. Comparatively, diminazene treatment was more effective in chronic infection than in early infection. In tandem, our study revealed that diminazene possesses anthelmintic properties and inhibits liver injury caused by Schistosoma eggs.