Pharmacofore design and virtual screening of dihydrofolate reductase of Schistossoma mansoni (SmDHFR)

• Grant number: 15/06513-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2015
• End date: August 07, 2016
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Gustavo Henrique Goulart Trossini
• Grantee: Cecilia Timm Wottrich
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Schistosomiasis is one of the leading causes of morbidity in tropical and subtropical countries, causing severe socioeconomics consequences. Nowadays, the available drugs for the treatment of schistosomiasis are praziquantel and oxamniquine, but reports of low susceptibility from the parasite to these drugs indicate the need of others therapeutic strategies for treatment of this disease. Nevertheless, there is not much concern in the pharmaceutical industry in the development of drugs against neglected tropical diseases, including schistosomiasis. Due to these factors, this project aims to identify new DHFR enzyme inhibitors candidates a antischistosomal drugs, through SmDHFR selective molecular interaction fields (MIFs)-based pharmacophore design and virtual screaning. To ensure the selective action of these molecules against the parasite's enzyme, molecular fields of selective interaction for SmDHFR will be employed at the construction of the pharmacophore model that will guide the virtual screening step. The computacional studies will guide the selection of 20 candidate molecules to SmDHFR inhibitors. So, it is expected that the results obtained at the end of this project may allow identifying a new class of potent and selective inhibitors of SmDHFR, that may be considered as prototypes for development of drugs against schistosomiasis.