Biochemical evaluation of a series of synthetic chalcone and hydrazide derivatives as novel inhibitors of cruzain from Trypanosoma cruzi

Journal of the Brazilian Chemical Society

Deise M. Borchhardt²  Alessandra Mascarello¹  Louise Domeneghini Chiaradia¹  Ricardo J. Nunes¹  Glaucius Oliva²  Rosendo A. Yunes¹  Adriano D. Andricopulo² 

[1] ,Universidade de São Paulo Instituto de Física de São Carlos Centro de Biotecnologia Molecular Estrutural

关键词: chalcones;    Trypanosoma cruzi;    cruzain;    Chagas' disease;    inhibition;   

DOI  :  10.1590/S0103-50532010000100021

来源: SciELO

【 摘 要 】

Chagas' disease, a parasitic infection widely distributed throughout Latin America, is a major public health problem with devastating consequences in terms of human morbidity and mortality. The enzyme cruzain is the major cysteine protease from Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas' disease, and has been selected as an attractive target for the development of novel trypanocidal drugs. In the present work, we describe the synthesis and inhibitory effects of a series of thirty-three chalcone and seven hydrazide derivatives against the enzyme cruzain from T. cruzi. Most of the compounds showed promising in vitro inhibition (IC50 values in the range of 20-60 μM), which suggest the potential of these compounds as lead candidates for further development. Twelve compounds have not been reported before, and four of them (7, 13, 16 e 18) are among the most potent inhibitors of the series.

【 授权许可】

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