Synthesis of benznidazole and graphene oxide derivatives and evaluation of their anti-chagasic activities

• Grant number: 20/00770-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2020
• End date: August 31, 2021
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Maria Carolina Quartim Barbosa Elias Sabbaga
• Grantee: Marcos Felipe Pinatto Botelho
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

This project aims, in general, to synthesize new derivatives of benznidazole, an anti-chagasic agent already used by ANVISA and FDA. The research is based on obtaining the desired derivatives, by the N-alkylation reaction of 2-nitro-imidazole, through sodium chloroacetate and subsequent acidification of the carboxylate, in order to obtain the carboxylic acid derivative. Another part of the project, similarly to the route described above, will be conducted with the 4-nitro-imidazole derivative to obtain new anti-chagasic derivatives that may be subjected to nitro group reduction and evaluation of its biological activity. With the derivatives in hand, it is intended to transform them into various amides by reaction with specific coupling agents and using amines and/or amino alcohols. The amides that have the alcohol functional group will be used in a new esterification reaction with succinic and/or glutaric anhydride, in order to obtain another carboxylic acid derivative, which will be used later in the project, in the functionalization of graphene oxide. In addition to obtaining benznidazole derivatives, including to testing their anti-chagasic activities, the project is based on the transformation of graphite into graphene oxide through oxidative procedures inherent to the technique of materials chemistry, leaving graphene oxide adapted to functionalization reactions with specific organic molecules. Initially the carboxylic acid groups of graphene oxide will be transformed into amides containing a free amino group. After this step, the main objective of the project is to couple the carboxylic acid derivatives, synthesized by the reaction with the anhydrides, with the free amino group inserted in the graphene oxide structure, in order to verify their activity against chagasic strains. (AU)