Design and Development of Drug Candidates for Chagas Disease

• Grant number: 13/25658-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2014
• End date: May 28, 2018
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Glaucius Oliva
• Grantee: Leonardo Luiz Gomes Ferreira
• 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
• Associated scholarship(s): 17/02763-2 - Phenotypic Screening and In vitro Metabolism Studies for Chagas Disease and leishmaniasis Drug Discovery, BE.EP.PD

Abstract

Chagas disease is a neglected tropical disease that reaches millions of people, especially in Latin America, where it is endemic. According to the World Health Organization (WHO) and the Drugs for Neglected Diseases Initiative (DNDi), Chagas disease occupies a position of high priority in their programs of research and development of new drugs. The available drugs are extremely limited and insufficient, characterized by low efficacy and high toxicity. In this context, the development of new, more effective and safe medicines is of paramount importance.The main goals of this project are the development and evaluation of new drug candidates for Chagas disease. The project is of utmost importance for the Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar, one of the CEPIDs supported by FAPESP), which has solid partnerships with UNICAMP and DNDi in order to develop drug candidates for neglected diseases such as leishmaniasis and Chagas disease. The project comprises methods of ligand-based drug design (LBDD); organic synthesis; in vitro biological evaluation against the parasite Trypanosoma cruzi and assays on culture of human cells to evaluate the selectivity of the compounds. Computational and experimental methods will be integrated in the process of molecular optimization of the compounds. The project will be developed in the Laboratory of Medicinal and Computational Chemistry (LQMC), at the Physics Institute of São Carlos (IFSC-USP) - the host institution of the CIBFar-CEPID/FAPESP.

Scientific publications

(14)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PAULI, IVANI; FERREIRA, LEONARDO G.; DE SOUZA, MARIANA L.; OLIVA, GLAUCIUS; FERREIRA, RAFAELA S.; DESSOY, MARCO A.; SLAFER, BRIAN W.; DIAS, LUIZ C.; ANDRICOPULO, ADRIANO D.. Molecular modeling and structure-activity relationships for a series of benzimidazole derivatives as cruzain inhibitors. Future Medicinal Chemistry, v. 9, n. 7, p. 641-657, MAY 2017. (11/13789-6, 13/07600-3, 13/25658-9)

FERREIRA, LEONARDO G.; OLIVA, GLAUCIUS; ANDRICOPULO, ADRIANO D.. From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery for Cancer and Neglected Tropical Diseases. Anais da Academia Brasileira de Ciências, v. 90, n. 1, 1, p. 645-661, 2018. (13/07600-3, 13/25658-9)

FERREIRA, LEONARDO G.; DOS SANTOS, RICARDO N.; OLIVA, GLAUCIUS; ANDRICOPULO, ADRIANO D.. Molecular Docking and Structure-Based Drug Design Strategies. Molecules, v. 20, n. 7, p. 13384-13421, JUL 2015. (13/07600-3, 13/25658-9)

FERREIRA, LEONARDO G.; ANDRICOPULO, ADRIANO D.. From Protein Structure to Small-Molecules: Recent Advances and Applications to Fragment-Based Drug Discovery. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 17, n. 20, p. 2260-2270, 2017. (13/07600-3, 13/25658-9)

MAFUD, ANA C.; FERREIRA, LEONARDO G.; MASCARENHAS, YVONNE P.; ANDRICOPULO, ADRIANO D.; DE MORAES, JOSUE. Discovery of Novel Antischistosomal Agents by Molecular Modeling Approaches. Trends in Parasitology, v. 32, n. 11, p. 874-886, NOV 2016. (14/02282-6, 13/25658-9, 13/07600-3)

FERREIRA, LEONARDO G.; OLIVA, GLAUCIUS; ANDRICOPULO, ADRIANO D.. Target-based molecular modeling strategies for schistosomiasis drug discovery. Future Medicinal Chemistry, v. 7, n. 6, p. 753-764, 2015. (13/07600-3, 13/25658-9)

FERREIRA, LEONARDO G.; DE OLIVEIRA, MARCELO T.; ANDRICOPULO, ADRIANO D.. Advances and Progress in Chagas Disease Drug Discovery. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 16, n. 20, p. 2290-2302, 2016. (13/07600-3, 13/25658-9)

FERREIRA, LEONARDO L. G.; FERREIRA, RAFAELA S.; PALOMINO, DAVID L.; ANDRICOPULO, ADRIANO D.. Structure-Based Virtual Screening and Biochemical Evaluation for the Identification of Novel Trypanosoma brucei Aldolase Inhibitors. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 18, n. 5, p. 397-405, 2018. (13/07600-3, 13/25658-9)

FERREIRA, LEONARDO G.; ANDRICOPULO, ADRIANO D.. Targeting cysteine proteases in trypanosomatid disease drug discovery. PHARMACOLOGY & THERAPEUTICS, v. 180, p. 49-61, DEC 2017. (13/07600-3, 13/25658-9)

MEDEIROS, ALEX R.; FERREIRA, LEONARDO L. G.; DE SOUZA, MARIANA L.; DE OLIVEIRA REZENDE JUNIOR, CELSO; ESPINOZA-CHAVEZ, ROCIO MARISOL; DIAS, LUIZ CARLOS; ANDRICOPULO, ADRIANO D.. hemoinformatics Studies on a Series of Imidazoles as Cruzain Inhibitor. BIOMOLECULES, v. 11, n. 4, APR 2021. (13/25658-9, 13/07600-3, 18/14268-9)

FERREIRA, LEONARDO L. G.; ANDRICOPULO, ADRIANO D.. Chemoinformatics Strategies for Leishmaniasis Drug Discovery. FRONTIERS IN PHARMACOLOGY, v. 9, NOV 1 2018. (13/25658-9, 13/07600-3)

FERREIRA, LEONARDO G.; ANDRICOPULO, ADRIANO D.. Fragment-Based QSAR and Structural Analysis of a Series of Hydroxyethylamine Derivatives as HIV-1 Protease Inhibitors. COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, v. 18, n. 5, p. 464-475, 2015. (13/07600-3, 13/25658-9)

FERREIRA, LEONARDO G.; OLIVA, GLAUCIUS; ANDRICOPULO, ADRIANO D.. Protein-protein interaction inhibitors: advances in anticancer drug design. EXPERT OPINION ON DRUG DISCOVERY, v. 11, n. 10, p. 957-968, OCT 2016. (13/07600-3, 13/25658-9)

ORTEGA, HUMBERTO E.; LOURENZON, VITOR B.; CHEVRETTE, MARC G.; FERREIRA, LEONARDO L. G.; ALVARENGA, RENE F. RAMOS; MELO, WEILAN G. P.; VENANCIO, TIAGO; CURRIE, CAMERON R.; ANDRICOPULO, ADRIANO D.; BUGNI, TIM S.; et al. Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311. Bioorganic & Medicinal Chemistry, v. 32, FEB 15 2021. (13/25658-9, 16/17614-0, 14/14095-6, 13/50954-0, 19/16559-3, 13/07600-3, 16/20154-0)