SYNTHESIS AND BIOLOGICAL EVALUATION OF 1,3,4-OXADIAZOLE AND 3H-IMIDAZO(4,5-C)PYRIDINE IN TRYPANOSOMATID LINEAGES.

• Grant number: 24/22317-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2025
• End date: July 31, 2027
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Júlio Cezar Pastre
• Grantee: Lucas Coral Ferreira
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/06661-5 - Enabling technologies for the sustainable chemical synthesis of platform molecules, new chemicals and bioactive compounds, AP.BIOEN.JP2

Abstract

Neglected tropical diseases (NTDs), named due to it affects tropical and subtropical regions and have not been targeted by major pharmaceutical companies, have been defined as a global concern by the World Health Organization (WHO). Among the diseases classified as NTDs, Chagas disease and Leishmaniasis were included, which account for thousands of cases and predominantly impact endemic regions. Caused by parasites of the Trypanosomatidae family, researching small molecules for the treatment of infections caused by these parasites remains challenging, despite extensive efforts to develop more effective therapies. Current drugs exhibit side effects, loss of efficacy due to resistance developed during prolonged treatments, or high costs, making them less accessible to low-income populations. The process of discovering new molecules in biological assays requires a large number of analogs. In this context, organic synthesis coupled with flow chemistry is promising, as it enables the fast synthesis of compound libraries and facilitates scaling, which is inherent to the technique. The present project aims to conduct structure-activity relationship (SAR) studies based on prototypes 18, containing the 3H-imidazo(4,5-c)pyridine core, and 19, containing the 1,2,4-oxadiazole core, previously provided by a pharmaceutical company to Prof. Dr. Adriano D. Andricopulo's group. After synthesizing structural analogs, we will evaluate them against two cell lines: MHOM/MA/67/ITMAP-263 (Leishmania infantum) and MHOM/CH/00/Tulahuen C2 (Trypanosoma cruzi), as well as determine their pharmacokinetic and pharmacodynamic parameters. To expedite the synthesis process, we will employ flow chemistry for the preparation of key intermediates. Through this proposal, which combines the collective efforts of laboratories with complementary expertise, we hope to contribute to the development of new and effective treatments for Chagas disease and leishmaniasis.