Artur Torres Cordeiro
Phone: +55 19 3512.1267
Leishmaniasis and trypanosomiasis are infectious neglected diseases caused by flagellated protozoan parasites transmitted to humans by hematophagous insects. The nutritional requirements of these parasites, once living in the bloodstream or inside human cells, are well known. Several enzymes involved in the parasite metabolism have been validated and pursued as targets for development of modern drugs.
My research interested is to combine HTS assays and protein crystallography of metabolic targets from parasites to discover and develop new drugs against neglected diseases.
Use HTS to discovery new inhibitors for human and parasites G6PDH
Glucose-6-phosphate dehydrogenase (G6PDH) catalyzes the first step of the pentose phosphate pathway, which supplies the cell with ribose-5-phosphate for synthesis of nucleotides and NADPH for biosynthesis of lipids, cholesterol and detoxification of reactive oxygen species. G6PDH is a validated molecular target against T. brucei bloodstream form, the causative agent of Sleep Sickness diseases. The aim of this project is to run HTS assays against the human, T. cruzi and Leismania mexicana G6PDHs in order to identify new hit compounds able to selective inhibit the parasite molecular target
Map the steroid binding site in the human and parasite G6PDH structure
Dehydroepiandrosterone (DHEA) is a steroidal “pro-hormone” known to inhibit mammalian G6PDHs in the micromolar range. Enzymatic assays done with G6PDH from others organisms suggested that only mammalian G6PDHs were inhibited by DHEA. We were the first research group to show an inhibitory effect of DHEA for non-mammalian G6PDHs. T. brucei and T. cruzi G6PDHs are uncompetitively inhibited by DHEA and some derivatives. Now, we intend to elucidate the crystallography structure for the G6PDH-DHEA complex in order to development new drugs against the parasite´s G6PDHs using Structure Based Drug Design methods.
Cordeiro, A.T., Feliciano, P.R., Pinheiro, M.P., Nonato, M.C. Crystal structure of dihydroorotate dehydrogenase from Leishmania major. Biochimie; 94(8):1739-48, 2012.
Mercaldi, G.F., Pereira, H.M., Cordeiro, A.T., Michels, P.A., Thiemann, O.H. Structural role of the active-site metal in the conformation of Trypanosoma brucei phosphoglycerate mutase. FEBS J.; 279(11):2012-21, 2012.
Gupta, S., Cordeiro, A. T., Michels, P.A.M.. Glucose-6-phosphate dehydrogenase is the target for the trypanocidal action of human steroids. Molecular and Biochemical Parasitology; 176:112-115, 2011.
Cordeiro, A. T., Thiemann, O. H. 16-Bromoepiandrosterone, an activator of the mammalian immune system, inhibits glucose 6-phosphate dehydrogenase from Trypanosoma cruzi and is toxic to these parasites grown in culture. Bioorganic & Medicinal Chemistry, 18:4762-4768, 2010.
Cordeiro, A.T., Thiemann, O.H., Michels, P.A. Inhibition of Trypanosoma brucei glucose-6-phosphate dehydrogenase by human steroids and their effects on the viability of cultured parasites. Bioorganic & Medicinal Chemistry. 17(6):2483-89, 2009.
PhD in Applied Physics, University of São Paulo, Brazil.
Graduated in Biological Sciences, University of Brasilia, Brazil.
OTHER PROFESSIONAL POSITIONS
Post-doc in the Research Unit for Tropical Diseases, de Duve Institute of Cellular Pathology, Brussels.