8-Methoxy-naphtho[2,3-b]thiophen-4,9-quinone, a non-competitive inhibitor of trypanothione reductase

Memórias do Instituto Oswaldo Cruz

Carlos L Zani²  Alan H Fairlamb¹ 

[1] ,Fiocruz Centro de Pesquisas René Rachou Laboratório de Química de Produtos NaturaisBelo Horizonte MG ,Brasil

关键词: trypanothione reductase;    Trypanosoma cruzi;    Leishmania;    enzyme inhibitors;    naphthoquinone;   

DOI  :  10.1590/S0074-02762003000400026

来源: SciELO

【 摘 要 】

The enzyme trypanothione reductase is a recognised drug target in trypanosomatids and has been used in the search of new compounds with potential activity against diseases such as leishmaniasis, Chagas disease and African trypanosomiasis. 8-Methoxy-naphtho [2,3-b] thiophen-4,9-quinone was selected in a screening of natural and synthetic compounds using an in vitro assay with the recombinant enzyme from Trypanosoma cruzi. Its mode of inhibition fits a non-competitive model with respect to the substrate (trypanothione) and to the co-factor (NADPH), with Ki-values of 5 and 3.6 µM, respectively. When tested against human glutathione reductase, this compound did not display any significant inhibition at 100 µM, indicating a good selectivity against the parasite enzyme.

【 授权许可】

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