Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

Author(s)

Porto, Raquel ^[1] ; Mengarda, Ana C. ^[1] ; Cajas, Rayssa A. ^[1] ; Salvadori, Maria C. ^[2] ; Teixeira, Fernanda S. ^[2] ; Arcanjo, Daniel D. R. ^[3] ; Siyadatpanah, Abolghasem ^[4] ; Pereira, Maria de Lourdes ^{[5, 6]} ; Wilairatana, Polrat ^[7] ; de Moraes, Josue ^[1]

Affiliation

^[1] Univ Guarulhos, Res Ctr Neglected Dis, Praca Tereza Cristina 229, BR-07023070 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Phys, BR-05508060 Sao Paulo, SP - Brazil

^[3] Univ Fed Piaui, Dept Physiol & Biophys, BR-64049550 Teresina, PI - Brazil

^[4] Birjand Univ Med Sci, Ferdows Sch Paramed & Hlth, Birjand 9717853577 - Iran

^[5] Univ Aveiro, CICECO Aveiro Inst, P-3810193 Aveiro - Portugal

^[6] Univ Aveiro, Dept Med Sci, P-3810193 Aveiro - Portugal

^[7] Mahidol Univ, Fac Trop Med, Dept Clin Trop Med, Bangkok 10400 - Thailand

• Document type: Journal article
• Source: PHARMACEUTICALS; v. 14, n. 7 JUL 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 16/22488-3 - Drug repositioning for neglected diseases: identification of novel anthelmintic agents
• Grantee: Josué de Moraes
• Support Opportunities: Regular Research Grants