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Phenotypic Screening and In vitro Metabolism Studies for Chagas Disease and leishmaniasis Drug Discovery

Grant number: 17/02763-2
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): May 01, 2017
Effective date (End): July 28, 2017
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Glaucius Oliva
Grantee:Leonardo Luiz Gomes Ferreira
Supervisor: Louis Maes
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Research place: University of Antwerp (UA), Belgium  
Associated to the scholarship:13/25658-9 - Design and Development of Drug Candidates for Chagas Disease, BP.PD


Chagas disease and leishmaniasis are infectious diseases caused by protozoan parasites of the genus Trypanosoma and Leishmania, respectively. Chagas disease is endemic in Latin America, affecting approximately 8 million people. Nearly 10,000 deaths occur each year as result of the clinical consequences of the disease. Leishmaniasis occurs in 98 countries and approximately 1.3 million new cases are registered each year, causing approximately 20,000 deaths. The available drugs for these conditions consist of a limited set of compounds that present a series of drawbacks. According to the Drugs for Neglected Diseases Initiative (DNDi), the shortcomings of these drugs demonstrate the need for novel therapeutic alternatives.The Laboratory of Medicinal and Computational Chemistry (LQMC) at the University of Sao Paulo is the headquarters of the Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), one of the Research, Innovation and Dissemination Centers (CEPID) supported by FAPESP. Recently, LQMC has joined the DNDi consortium becoming one of the network centers dedicated to drug design and screening within the Lead Optimization Latin America program (LOLA). Through this consortium, LQMC participates in the worldwide coordinated efforts to discover new drug candidates for Chagas disease and leishmaniasis. The aim of this internship proposal is to develop a phenotypic screening strategy against Trypanosoma cruzi, Leishmania infantum and human cells, along with in vitro metabolic stability studies for a series of compounds developed at LQMC. All of these analyses will be conducted in the Laboratory of Microbiology, Parasitology and Hygiene (LMPH) at the University of Antwerp in Belgium. LMPH is a center of excellence in the development of experimental screening methods for tropical diseases such as Chagas disease, leishmaniasis and sleeping sickness, and also for bacterial and fungal infections. The broad spectrum of assays developed at LMPH include anti-parasitic, cytotoxicity and pharmacokinetics evaluations and are highly complementary to the drug design activities performed at LQMC. In this context, an internship of 5 months (from May 1st to Sep 30th) is proposed comprising the mobility of Dr. Leonardo Ferreira to LMPH to conduct research activities under the supervision of Prof. Louis Maes, who is the head of LMPH and of Prof. Guy Caljon, research professor at LMPH. The main goal of the project is to determine the biological activity of a novel series of compounds against T. cruzi and L. infantum (especially intracellular forms) as well as cytotoxicity against human cells. A subset comprising the most active compounds will be evaluated for pharmacokinetics involving in vitro metabolic stability studies. The candidate will be trained in all of these procedures at LPMH and then bring the expertise to LQMC, where these methods are to be fully implemented.

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