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Potential antitripanosomal derived from nitro-heterocyclic compounds

Grant number: 01/01192-3
Support type:Research Projects - Thematic Grants
Duration: July 01, 2002 - April 30, 2010
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Elizabeth Igne Ferreira
Grantee:Elizabeth Igne Ferreira
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Antonia Tavares Do Amaral ; Silvia Helena Pires Serrano
Associated scholarship(s):08/07296-4 - Design, synthesis, evaluation of biological activity against Trypanosoma cruzi and QSAR studies of a series of oxadiazolines compounds, BP.PD


Chagas' disease is endemic for most of Latin America, serioulsy affectinq the health of infected people and shortening their lives. Around 16 to 18 million people are estimated to be infected and about 50 thousands of deaths are registered each year in the 21 endemic countries. The therapeutic armamentarium against the parasitosis is scarce, as only two drugs have been used, none of them sufficiently effective at the cronic stage of this disease. Considering that only people from underdeveloped countries are inffected or under the risk of contracting the parasitosis, the interest is relatively low to the countries responsible for the introduction of most part of druqs in the therapeutics. Thus, searching for new drugs against the disease is mainly a task for those underdeveloped countries, from the above, and taking into account the high activity showed by nitro-heterocyclic derivatives that have been already synthesized by our group, and/or others using diverse approaches, our main goal is to find new and effective drug candidates among this class of compounds. This objective will necessarily be supported by in vitro and in vivo assays, besides by mutagenicity tests. The study of mechanism of action of those candidates through electrochemical methodologies, as using biosensors with immobilized nucleic acids and enzymes, and the elucidation of chemical structure-biological activity (QSAR), especially 3D-QSAR, assisted by molecular modeling, are the rational bases for the design of new and more effective nitro-heterocyclic derivatives. We hope to contribute in a integrated way to the search for better antitripanosomal agents. (AU)

Scientific publications (22)
(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)
SANTOS, SORAYA DA SILVA; GIAROLLA, JEANINE; PASQUALOTO, KERLY F. M.; FERREIRA, ELIZABETH I. Molecular modelling as a tool for studying the disassembly of potentially leishmanicide-targeted dendrimer. MOLECULAR SIMULATION, v. 39, n. 11, p. 860-867, SEP 1 2013. Web of Science Citations: 3.
GIAROLLA, JEANINE; PASQUALOTO, KERLY F. M.; RANDO, DANIELA G.; ZAIM, MARCIO H.; FERREIRA, ELIZABETH I. Molecular modeling study on the disassembly of dendrimers designed as potential antichagasic and antileishmanial prodrugs. Journal of Molecular Modeling, v. 18, n. 5, p. 2257-2269, MAY 2012. Web of Science Citations: 7.
GOULART TROSSINI, GUSTAVO HENRIQUE; CHIN, CHUNG MAN; DE SOUZA MENEZES, CARLA MARIA; FERREIRA, ELIZABETH IGNE. Molecular Modeling Suggests Cruzain Specificity for Peptide Primaquine Prodrugs. LETTERS IN DRUG DESIGN & DISCOVERY, v. 7, n. 7, p. 528-533, AUG 2010. Web of Science Citations: 4.
RANDO, DANIELA GONCALVES; GIAROLLA, JEANINE; MESQUITA PASQUALOTO, KERLY FERNANDA; FERREIRA, ELIZABETH IGNE. Chalcones and N-acylhydrazones: direct analogues? Exploratory data analysis applied to potential novel antileishmanial agents. Brazilian Journal of Pharmaceutical Sciences, v. 46, n. 2, p. 311-321, APR-JUN 2010. Web of Science Citations: 3.
TROSSINI, GUSTAVO H. G.; GIAROLLA, JEANINE; DE REZENDE, LEANDRO; DO AMARAL, ANTONIA T.; ZAIM, MARCIO H.; BRUNS, ROY E.; FERREIRA, ELIZABETH I. Synthesis Optimization of Hydroxymethylnitrofurazone, an Antichagasic Candidate, Using 3(2) Factorial Design. Letters in Organic Chemistry, v. 7, n. 3, p. 191-195, APR 2010. Web of Science Citations: 6.
TROSSINI, GUSTAVO H. G.; MALVEZZI, ALBERTO; T-DO AMARAL, ANTONIA; RANGEL-YAGUI, CARLOTA OLIVEIRA; IZIDORO, MARIO A.; CEZARI, MARIA HELENA S.; JULIANO, LUIZ; CHIN, CHUNG MAN; MENEZES, CARLA M. S.; FERREIRA, ELIZABETH IGNE. Cruzain inhibition by hydroxymethylnitrofurazone and nitrofurazone: investigation of a new target in Trypanosoma cruzi. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 25, n. 1, p. 62-67, FEB 2010. Web of Science Citations: 23.
GIAROLLA, JEANINE; RANDO, DANIELA G.; PASQUALOTO, KERLY F. M.; ZAIM, MARCIO H.; FERREIRA, ELIZABETH I. Molecular modeling as a promising tool to study dendrimer prodrugs delivery. JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, v. 939, n. 1-3, p. 133-138, JAN 15 2010. Web of Science Citations: 10.
PAULA, FAVERO R.; TROSSINI, GUSTAVO H. G.; FERREIRA, ELIZABETH I.; SERRANO, SILVIA H. P.; MENEZES, CARLA M. S.; TAVARES, LEOBERTO C. Theoretical and Voltammetric Studies of 5-Nitro-heterocyclic Derivatives with Potential Trypanocidal Activities. Journal of the Brazilian Chemical Society, v. 21, n. 4, p. 740-749, 2010. Web of Science Citations: 5.
ISHIKI, HAMILTON MITSUGU; DO AMARAL, ANTONIA T. Three-Dimensional Quantitative Structure-Activity Relationship Study of Antitumor 2-Formylpyridine Thiosemicarbazones Derivatives as Inhibitors of Ribonucleotide Reductase. QSAR & COMBINATORIAL SCIENCE, v. 28, n. 11-12, p. 1334-1345, DEC 2009. Web of Science Citations: 3.
LA-SCALEA, M. A.; TROSSINI, G. H. G.; MENEZES, C. M. S.; CHUNG, M. C.; FERREIRA, E. I. Electrochemical Reduction Using Glassy Carbon Electrode in Aqueous Medium of a Potential Anti-Chagas Drug: NFOH. Journal of the Electrochemical Society, v. 156, n. 7, p. F93-F97, 2009. Web of Science Citations: 8.
MALVEZZI‚ A.; DE REZENDE‚ L.; AMARAL‚ A.T.; OTHERS. Pharmacophore Model of Cruzain Inhibitors. QSAR & COMBINATORIAL SCIENCE, v. 28, n. 8, p. 781-784, 2009.
FERREIRA, ELIZABETH IGNE; MALVEZZI, ALBERTO; REZENDE, LEANDRO DE; IZIDORO, MARIO AUGUSTO; CEZARI, MARIA HELENA SEDENHO; JULIANO, LUIZ; AMARAL, ANTONIA T. -DO. Uncovering false positives on a virtual screening search for cruzain inhibitors. Bioorganic & Medicinal Chemistry Letters, v. 18, n. 1, p. 350-354, Jan. 2008.
DA SILVA‚ R.P.; LIMA‚ A.W.O.; SERRANO‚ S.H.P. Simultaneous voltammetric detection of ascorbic acid‚ dopamine and uric acid using a pyrolytic graphite electrode modified into dopamine solution. Analytica Chimica Acta, v. 612, n. 1, p. 89-98, 2008.
GUIDO, RAFAEL V. C.; TROSSINI, GUSTAVO H. G.; CASTILHO, MARCELO S.; OLIVA, GLAUCIUS; FERREIRA, ELIZABETH I.; ANDRICOPULO, ADRIANO D. Structure-activity relationships for a class of selective inhibitors of the major cysteine protease from Trypanosoma cruzi. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 23, n. 6, p. 964-973, 2008. Web of Science Citations: 26.
BARBOSA, C. F.; OKUDA, E. S.; CHUNG, M. C.; FERREIRA, E. I.; CICARELLI, R. M. B. Rapid test for the evaluation of the activity of the prodrug hydroxymethylnitrofurazone in the processing of Trypanosoma cruzi messenger RNAs. Brazilian Journal of Medical and Biological Research, v. 40, n. 1, p. 33-39, Jan. 2007.
JULIÃO, MURILO S. DA S.; FERREIRA, ELIZABETH I.; FERREIRA, NEIDENÊI G.; SERRANO, SILVIA H. P. Voltammetric detection of the interactions between RNO2 circle- and electron acceptors in aqueous medium at highly boron doped diamond electrode (HBDDE). Electrochimica Acta, v. 51, n. 24, p. 5080-5086, July 2006.
LA-SCALEA, MAURO A.; MENEZES, CARLA M. S.; MATSUTAMI, GUILHERME C.; POLLI, MICHELLE C.; SERRANO, SÍLVIA H. P.; FERREIRA, ELIZABETH I. Molecular modeling of the voltammetric oxidation at a glassy carbon electrode of the antimalarial drug primaquine and its prodrugs succinylprimaquine and maleylprimaquine. Electrochimica Acta, v. 51, n. 24, p. 5103-5111, July 2006.
LORENA BLAU; RENATO FARINA MENEGON; MAN CHIN CHUNG. Pró-fármaco ativado por enzima, uma estratégia promissora na quimioterapia. Química Nova, v. 29, n. 6, p. 1307-1317, Dez. 2006.
LA-SCALEA, MAURO AQUILES; MENEZES, CARLA MARIA DE SOUZA; JULIÃO, MURILO SÉRGIO DA SILVA; CHUNG, MAN CHIN; SERRANO, SÍLVIA HELENA PIRES; FERREIRA, ELIZABETH IGNE. Voltammetric behavior of nitrofurazone and its hydroxymethyl prodrug with potential anti-Chagas activity. Journal of the Brazilian Chemical Society, v. 16, n. 4, p. 774-782, jul./ago. 2005.
JULIÃO, MURILO SÉRGIO DA SILVA; ALMEIDA, ÉRICA CRISTINA; LA SCALEA, MAURO AQUILES; FERREIRA, NEIDENÊI GOMES; COMPTON, RICHARD G.; SERRANO, SÍLVIA HELENA PIRES. Voltammetric behavior of nitrofurazone at highly boron doped diamond electrode. Electroanalysis, v. 17, n. 3, p. 269-274, Feb. 2005.
CHUNG, MAN-CHIN; GUIDO, RAFAEL VICTÓRIO CARVALHO; MARTINELLI, TATIANE FAVARATO; GONÇALVES, MARINEI FERREIRA; POLLI, MICHELLE CARNEIRO; BOTELHO, KATIA CIRLENE ALVES; VARANDA, ELIANA APARECIDA; COLLI, WALTER; MIRANDA, M. TERÊSA M.; FERREIRA, ELIZABETH IGNE. Synthesis and in vitro evaluation of potential antichagasic hydroxymethyinitrofurazone (NFOH-121): A new nitrofurazone prodrug. Bioorganic & Medicinal Chemistry, v. 11, n. 22, p. 4779-4783, Nov. 2003.
BRACCO‚ ME; CHIAPPARINI‚ M.; LOZEA‚ A.; NAVARRA‚ FS; NIELSEN‚ M. D and [rho] mesons: who resolves whom?. Physics Letters B, v. 521, n. 1-2, p. 1-6, 2001.

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Filed patent(s) as a result of this research project

PRÓ-FÁRMACO DENDRIMÉRICO, PROCESSO PARA SUA PREPARAÇÃO E COMPOSIÇÕES CONTENDO OS MESMOS PI0705122-0 - Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Universidade de São Paulo (USP) . Elizabeth Igne Ferreira; Jeanine Giarolla - October 2007, 17