Planning and synthesis of boronic derivatives acylhydrazones as antichagasic agents

• Grant number: 23/08687-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2023
• End date: February 03, 2025
• 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
• Associated scholarship(s): 23/15774-3 - Biodistribuition study of new boron based compounds as anti-chagas agents using DESI-MS imaging, BE.EP.IC

Abstract

Chagas disease, also known as American trypanosomiasis, is currently considered one of the 17 neglected tropical diseases, causing approximately 8,000,000 to 10,000,000 infections worldwide. The parasite responsible for the infection is Trypanosoma cruzi, which leads to various lesions in the host's organism, such as cardiomegaly, megacolon, and hepatosplenomegaly. Currently, there is no approved effective treatment for Chagas disease in Brazil, making its treatment extremely challenging. The parasite's life cycle is characterized by several morphological transformations, where specific enzymes and proteins are responsible for maintaining the parasite within the host, such as nitroreductases, squalene synthases, cysteine proteases, and cleavage and polyadenylation factors. Based on derivatives of hydrazones, a group of privileged structures, and boronic derivatives, which are important groups in medicinal chemistry, this project proposes the synthesis of compounds that, through molecular modifications based on computational methods, aim to inhibit the parasite's life cycle. The discovery and study of new compounds are fundamental for elucidating the molecule's interactions with its target, optimizing the understanding of specific inhibitors, and the comprehension of key chemical groups in the treatment of Chagas disease.