abstract
The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 mu M. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.
keywords
ANTISCHISTOSOMAL AGENTS; DRUGS; AMIODARONE; CHANNELS; RECEPTOR
subject category
Chemistry, Medicinal; Pharmacology & Pharmacy
authors
Porto, R; Mengarda, AC; Cajas, RA; Salvadori, MC; Teixeira, FS; Arcanjo, DDR; Siyadatpanah, A; Pereira, MD; Wilairatana, P; de Moraes, J
our authors
Maria de Lourdes Gomes Pereira
Associate Professor with Aggregationacknowledgements
This research was funded by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), grant number 2016/22488-3. The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.