Chemoinformatics strategies for a series of antichagasic compounds

• Grant number: 17/23778-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2018
• Effective date (End): July 31, 2018
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Adriano Defini Andricopulo
• Grantee: Alex Rogério Medeiros
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

Chagas disease is a neglected tropical disease that affects millions of people worldwide, mainly in Latin America, where it is endemic. According to the World Health Organization, Chagas disease is a high priority condition for the development of novel therapies. The available drugs are obsolete, and have low efficacy and outstanding toxicity. In this context, the discovery of novel treatments for Chagas disease is an urgent demand, particularly in endemic countries such as Brazil.The goal of this project is the design of novel drug candidates for Chagas disease. Promising compounds, highly active against the etiological agent of the disease (the protozoan Trypanosoma cruzi), identified in our laboratory, will be used in the designing process. These molecules are potent inhibitors of cruzain, the major cysteine protease of T. cruzi, which is an essential enzyme for its reproduction and pathogenicity. The project is important for the Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar - CEPID) supported by FAPESP, which has solid partnerships with UNICAMP and the Drugs for Neglected Diseases Initiative (DNDi) for the development of drug candidates for Chagas disease. The project includes the use of ligand-based drug design strategies (LBDD), such as the generation of Quantitative-Structure Activity Relationship models (QSAR) e pharmacophore modeling. The project will be conducted at the Laboratory of Medicinal and Computational Chemistry (LQMC) of the Physics Institute of Sao Carlos, University of Sao Paulo (IFSC - USP). LQMC has an important background in the field of drug design for Chagas disease, which culminated in the establishment of CIBFar. This project is fully integrated with the activities of CIBFar and will contribute to the advance of our research in a therapeutic field that is a major public health problem in Latin America. (AU)