8-Methoxy-naphtho[2,3-6]thiophen-4,9-quinone, a Non-competitive Inhibitor of Trypanothione Reductase

Carlos L. Zani; Alan H. Fairlamb

doi:10.1590/S0074-02762003000400026

8-Methoxy-naphtho[2,3-6]thiophen-4,9-quinone, a Non-competitive Inhibitor of Trypanothione Reductase

Carlos L. Zani, Alan H. Fairlamb

Biological Chemistry and Drug Discovery

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	565-568
Number of pages	4
Journal	Memorias do Instituto Oswaldo Cruz
Volume	98
Issue number	4
DOIs	https://doi.org/10.1590/S0074-02762003000400026
Publication status	Published - Jun 2003

Keywords

Enzyme inhibitors
Leishmania
Naphthoquinone
Trypanosoma cruzi
Trypanothione reductase

ASJC Scopus subject areas

Microbiology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1590/S0074-02762003000400026

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abstract = "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.",

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AU - Fairlamb, Alan H.

PY - 2003/6

Y1 - 2003/6

N2 - 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.

AB - 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.

KW - Enzyme inhibitors

KW - Leishmania

KW - Naphthoquinone

KW - Trypanosoma cruzi

KW - Trypanothione reductase

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8-Methoxy-naphtho[2,3-6]thiophen-4,9-quinone, a Non-competitive Inhibitor of Trypanothione Reductase

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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