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Hydroxymethylnitrofurazone (NFOH): activity study in chronic phase of Chagas' Disease in an animal model and synthesis of soluble derivatives

Grant number: 16/10847-9
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2018
Effective date (End): March 28, 2020
Field of knowledge:Health Sciences - Pharmacy - Medicines Analysis and Control
Principal Investigator:Chung Man Chin
Grantee:Cauê Benito Scarim
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


Chagas Disease is a major public health problems in Latin America. In Brazil, only benznidazole (BNZ) is available for the treatment of the disease, being active only in the acute phase. Research with hydroxymethylnitrofurazone (NFOH) showed that this compound has anti T. cruzi activity in vitro and in vivo with low toxicity in mutagenicity assays and LD50. Scarim (2016) standardized a methodology for testing in chronic phase, with immunosuppression in an animal model, having conducted the study with the Y strain and observed negative parasitaemia for NFOH and BNZ, but with the presence of amastigotes niches in the heart and liver to the BZN group and not for the NFOH. Thus, this work proposes the test of NFOH in chronic phase in animals infected with T. cruzi strain Bolivia. Also, due to the low solubility of NFOH and based on studies on the occurrence of inflammation during the chronic phase and knowledge of taurine as water soluble amino acid with potential anti-inflammatory and antioxidant, this project aims also the design and synthesis of two water soluble derivatives of NFOH and taurine, the evaluation of trypanocidal activity in amastigotes form in a in vitro assay and later evaluate the activity in a in vivo model-based image, at Skaggs School of Pharmacy and Pharmaceutical Sciences, US San Diego, USA as part of sandwich internship under the supervision of Prof. Dr Jair Lage Siqueira Neto. (AU)

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Scientific publications (7)
(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)
SCARIM, CAUE B.; CHELUCCI, RAFAEL C.; DOS SANTOS, JEAN L.; CHIN, CHUNG M.. The Use of Sulfonamide Derivatives in the Treatment of Trypanosomatid Parasites including Trypanosoma cruzi, Trypanosoma brucei, and Leishmania ssp. Medicinal Chemistry, v. 16, n. 1, p. 24-38, . (16/10847-9)
SCARIM, CAUE BENITO; CHIN, CHUNG MAN. Nitroheterocyclic derivatives: privileged scaffold for drug development against Chagas disease. MEDICINAL CHEMISTRY RESEARCH, v. 28, n. 12, p. 2099-2108, . (16/10847-9)
SCARIM, CAUE B.; CHIN, CHUNG M.. Current Approaches to Drug Discovery for Chagas Disease: Methodological Advances. COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, v. 22, n. 8, p. 509-520, . (16/10847-9)
SCARIM, CAUE BENITO; JORNADA, DANIELA HARTMANN; MENDES MACHADO, MARCELLA GABRIELLE; RIBERIO FERREIRA, CARLA MARIA; DOS SANTOS, JEAN LEANDRO; CHUNG, MAN CHIN. Thiazole, thio and semicarbazone derivatives against tropical infective diseases: Chagas disease, human African trypanosomiasis (HAT), leishmaniasis, and malaria. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 162, p. 378-395, . (16/10847-9)
SCARIM, CAUE BENITO; DE FARIAS, RENAN LIRA; DE GODOY NETTO, ADELINO VIEIRA; CHIN, CHUNG MAN; DOS SANTOS, JEAN LEANDRO; PAVAN, FERNANDO ROGERIO. Recent advances in drug discovery against Mycobacterium tuberculosis: Metal-based complexes. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 214, . (16/10847-9)
CAUÊ BENITO SCARIM; CLEVERTON ROBERTO DE ANDRADE; ROSSANA FALCONE; LETÍCIA MORENO AMBROZINI; VITOR IZIDORO SENHORELLI; JOÃO ARISTEU DA ROSA; CHUNG MAN CHIN. Hydroxymethylnitrofurazone (NFOH) decreases parasitaemia, parasitism and tissue lesion caused by infection with the Bolivia Trypanosoma cruzi type I strain in Swiss and C57BL/6 mice. Brazilian Journal of Pharmaceutical Sciences, v. 58, . (16/10847-9)
SCARIM, CAUE BENITO; OLMO, FRANCISCO; FERREIRA, ELIZABETH IGNE; CHIN, CHUNG MAN; KELLY, JOHN M.; FORTES FRANCISCO, AMANDA. Image-Based In Vitro Screening Reveals the Trypanostatic Activity of Hydroxymethylnitrofurazone against Trypanosoma cruzi. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 13, . (16/10847-9)

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