Study of the in vitro effects of palladacicles compounds on Schistosoma mansoni adult worms

• Grant number: 18/20935-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2019
• End date: December 31, 2019
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Katia Cristina Pereira Oliveira Santos
• Grantee: Camila Banca Guedes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Schistosomiasis is a neglected parasitic disease caused by the S. mansoni, a trematode that affects 200 million individuals in 76 countries. The parasite has a complex biological cycle, with six distinct stages of development and two hosts, one intermediate (mollusk) and one definitive (man). The treatment of schistosomiasis is performed by the oral administration of praziquantel that has low toxicity, is very efficient in the elimination of adult worms, but there are some parasite strains resistant to this drug. This resistance is favored by mass treatment routinely performed in endemic regions. In this context, the search for new therapeutic alternatives is important and necessary. It has already been shown that the palladacycle complexes DPPE 1.1 and DPPE 1.2 have leishmanicidal activity; low toxicity and inhibit the activity of cysteine proteinases, specifically cathepsin B of Leishmania spp. Cathepsin B is a pathogenicity factor of S. mansoni, as it is responsible for most of the hemoglobin hydrolysis, the main source of amino acids of the parasite, and it has been shown that the inhibition of this enzyme causes a delay in the development and limitation of the viability of this helminth. Within this approach, it is believed that the palladacycle compounds have a potential schistosomicidal activity. In this context, the objective of this proposal is to study the possible effects of the palladacycle compounds on the stages of adult worms and schistosomula of the S. mansoni. It is expected that, as observed in Leishmania (Leishmania) amazonensis, the exposure of S. mansoni to these palladacycle complexes results in compromised parasite viability. This will allow exploring the use of DPPE 1.1 and DPPE 1.2 as a new therapeutic approach in the fight against schistosomiasis and as a tool to elucidate the role of cathepsin B in parasite development.