8-Methoxy-naphtho[2,3-b]thiophen-4,9-quinone, a non-competitive inhibitor of trypanothione reductase.
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  M, respectively. When tested against human glutathione reductase, this compound did not display any significant inhibition at 100  M, indicating a good selectivity against the parasite enzyme.
Zani
Carlos L
CL
Laboratório de Química de Produtos Naturais, Centro de Pesquisas Ren Rachou, Fiocruz, Belo Horizonte, MG, 30190-002, Brasil. zani@cpqrr.fiocruz.br
Fairlamb
Alan H
AH
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009249:NADP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021261:Parasitic Sensitivity Tests; D011809:Quinones / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology*
C478222:8-methoxy-naphtho(2,3-b)thiophen-4,9-quinone; D004791:Enzyme Inhibitors; D011809:Quinones; D009249:NADP; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase