On the search for potential anti-Trypanosoma cruzi drugs: Synthesis and biological evaluation of 2-hydroxy-3-methylamino and 1,2,3-triazolic naphthoquinoidal compounds obtained by click chemistry reactions

Autor(es):Mostrar menos -

da Silva Junior, Eufranio N. ^[1] ; de Melo, Isadora M. M. ^[1] ; Diogo, Emilay B. T. ^[1] ; Costa, Verenice A. ^[1] ; de Souza Filho, Jose D. ^[1] ; Valenca, Wagner O. ^[2] ; Camara, Celso A. ^[2] ; de Oliveira, Ronaldo N. ^[2] ; de Araujo, Alexandre S. ^[3] ; Emery, Flavio S. ^[4] ; dos Santos, Marcelo R. ^[5] ; de Simone, Carlos A. ^[6] ; Menna-Barreto, Rubem F. S. ^[7] ; de Castro, Solange L. ^[7]

Afiliação do(s) autor(es)

^[1] Univ Fed Minas Gerais, Lab Quim Sintet & Heterocicl, Inst Ciencias Exatas, Dept Quim, BR-31270901 Belo Horizonte, MG - Brazil

^[2] Univ Fed Rural Pernambuco, Dept Ciencias Mol, BR-52171900 Recife, PE - Brazil

^[3] UNESP, Inst Biociencias Letras & Ciencias Exatas Sao Jos, Dept Fis, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut, BR-14040903 Sao Paulo - Brazil

^[5] Univ Brasilia, Inst Quim, BR-70910970 Brasilia, DF - Brazil

^[6] Univ Sao Paulo, Dept Fis & Informat, Inst Fis, BR-13560160 Sao Carlos, SP - Brazil

^[7] Fiocruz MS, Lab Biol Celular, Inst Oswaldo Cruz, BR-21045900 Rio De Janeiro, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 52, p. 304-312, JUN 2012.
• Citações Web of Science: 42

Resumo

Five 2-hydroxy-3-substituted-aminomethyl naphthoquinones, nine 1,2,3-triazolic para-naphthoquinones, five nor-beta-lapachone-based 1,2,3-triazoles, and several other naphthoquinonoid compounds were synthesized and evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease, continuing our screening program for new trypanocidal compounds. Among all the substances, 16-18, 23, 25-29 and 30-33 were herein described for the first time and fifteen substances were identified as more potent than the standard drug benznidazole, with IC50/24 h values in the range of 10.9-101.5 mu M. Compounds 14 and 19 with Selectivity Index of 18.9 and 6.1 are important structures for further studies. (C) 2012 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 09/51812-0 - Desenvolvimento de uma plataforma para o estudo do metabolismo in vivo e in vitro de produtos naturais, uma necessidade para o sistema de ensaios pré-clínicos
• Beneficiário: Norberto Peporine Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 09/14184-0 - Agentes anti-infecciosos: congregando a química medicinal e síntese orgânica na busca de protótipos antiparasitários
• Beneficiário: Flavio da Silva Emery
• Modalidade de apoio: Auxílio à Pesquisa - Regular