Design, synthesis and characterization of benzofuroxanes coupled to alpha, beta unsaturated carbonyls as cruzain inhibitors

• Grant number: 23/02276-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2023
• End date: June 30, 2024
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Cauê Benito Scarim
• Grantee: Pamela Souza Tada da Cunha
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Chagas disease, even than a century after its discovery (1909), is still a major public health problem. It is estimated that approximately 10 million people worldwide are infected with Trypanosoma cruzi (T. cruzi). However, the situation is more critical in Latin America and other regions where this disease is endemic. The largest number of cases occurs in Brazil, Bolivia, Argentina and Mexico, as well as more than 100 million people in these regions are located in areas with a high risk of contamination by the vector. The need for new therapeutic alternatives is urgent, once that the available drugs have severe limitations such as low efficacy and high toxicity. Based on this scenario, in this work, we employed a virtual screening technique using the T. cruzi cysteine protease (cruzain) as a biological target, key to the survival of the parasite. From derivatives of ±, ² unsaturated carbonyls, which are promising and important compounds in the medicinal chemistry field, this project proposes the synthesis of compounds, with molecular modifications based on computational methods, aimed at inhibiting cruzain. The discovery of new compounds are fundamental for elucidating the interactions of the molecule with its target, optimizing the understanding of specific inhibitors and the moieties for the treatment of Chagas disease.