Planning and Synthesis of Benzoboroxole Derivatives and 5-Furan-2-Substituted N-Acylhydrazones as Novel Anti-Chagasic Agents

• Grant number: 24/18020-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Chung Man Chin
• Grantee: Diogo Boreski
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Chagas disease, also known as American trypanosomiasis, is one of the 17 globally recognized neglected tropical diseases. It is estimated to affect between 8 to 10 million people worldwide. The causative agent is the Trypanosoma cruzi parasite, which can lead to severe complications in the host's body, including cardiomegaly, megacolon, and hepatosplenomegaly. In Brazil, there is no approved effective treatment for Chagas disease, making disease management significantly challenging. The life cycle of T. cruzi is marked by various morphological transformations, where specific enzymes, such as nitroreductases, squalene synthases, cysteine proteases, and cleavage and polyadenylation factors, play crucial roles in the parasite's survival within the host. This project aims to synthesize new compounds with antiparasitic potential, targeting trypanothione reductase and specific endonucleases of the parasite, by utilizing molecular modifications and computational methods with derivatives of furan and benzoxaborole N-acyl hydrazones. The goal is to develop active molecules that inhibit the life cycle of T. cruzi. Research and development of new compounds are vital to understanding how these molecules interact with biological targets and optimizing specific inhibitors for Chagas disease and other neglected tropical diseases.