Antischistosomal properties of aurone derivatives against juvenile and adult worms of Schistosoma mansoni

Author(s):Show less -

Pereira, Vinicius R. D. ^[1] ; da Silveira, Ligia S. ^[2] ; Mengarda, Ana C. ^[3] ; Alves Junior, Ismael J. ^[1] ; Zuza da Silva, Ohana Oliveira ^[1] ; Miguel, Fabio Balbino ^[2] ; Silva, Marcos P. ^[3] ; Almeida, Ayla das C. ^[4] ; Torres, Daniel da Silva ^[4] ; Pinto, Priscila de F. ^[4] ; Coimbra, Elaine S. ^[4] ; de Moraes, Josue ^[3] ; Couri, Mara R. C. ^[2] ; da Silva Filho, Ademar A. ^[1]

Affiliation

^[1] Univ Fed Juiz de Fora, Fac Farm, Dept Ciencias Farmaceut, R Jose Lourenco Kelmer S-N, Campus Univ, BR-36036900 Juiz De Fora, MG - Brazil

^[2] Univ Fed Juiz de Fora, Dept Quim, BR-36036900 Juiz De Fora, MG - Brazil

^[3] Univ Guarulhos, Nucleo Pesquisa Doencas Negligenciadas, BR-07023070 Guarulhos, SP - Brazil

^[4] Univ Fed Juiz de Fora, Inst Ciencias Biol, BR-36036900 Juiz De Fora, MG - Brazil

• Document type: Journal article
• Source: Acta Tropica; v. 213, JAN 2021.
• Web of Science Citations: 0

Abstract

Schistosomiasis is a neglected disease caused by helminth flatworms of the genus Schistosoma, affecting over 240 million people in more than 70 countries. The treatment relies on a single drug, praziquantel, making urgent the discovery of new compounds. Aurones are a natural type of flavonoids that display interesting pharmacological activities, particularly as chemotherapeutic agents against parasites. In pursuit of treatment alternatives, the present work conducted an in vitro and in vivo antischistosomal investigation with aurone derivatives against Schistosoma mansoni. After preparation of aurone derivatives and their in vitro evaluation on adult schistosomes, the three most active aurones were evaluated in cytotoxicity and haemolytic assays, as well as in confocal laser scanning microscope studies, showing tegumental damage in parasites in a concentration-dependent manner with no haemolytic or cytotoxic potential toward mammalian cells. In a mouse model of schistosomiasis, at a single oral dose of 400 mg/kg, the selected aurones showed worm burden reductions of 35% to 65.0% and egg reductions of 25% to 70.0%. The most active thiophenyl aurone derivative 18, unlike PZQ, had efficacy in mice harboring juvenile S. mansoni, also showing significant inhibition of oviposition by parasites, giving support for the antiparasitic potential of aurones as lead compounds for novel antischistosomal drugs. (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