Arylfurans as potential Trypanosoma cruzi trypanothione reductase inhibitors

• Published in: Memórias do Instituto Oswaldo Cruz Vol. 101; no. 2; pp. 169 - 173
• Main Authors: de Oliveira, Renata B, Vaz, Aline B M, Alves, Rosana O, Liarte, Daniel B, Donnici, Claudio L, Romanha, Alvaro J, Zani, Carlos L
• Format: Journal Article
• Language: English
• Published: Brazil Fundação Oswaldo Cruz, Fiocruz 01-03-2006; Instituto Oswaldo Cruz, Ministério da Saúde; Fundação Oswaldo Cruz (FIOCRUZ)
• Subjects: Animals; arylfurans; Chagas disease; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Furans - chemistry; Furans - pharmacology; Inhibitory Concentration 50; Male; Mice; NADH, NADPH Oxidoreductases - antagonists & inhibitors; PARASITOLOGY; Structure-Activity Relationship; tropical diseases; tropical diseases - Chagas disease - arylfurans - trypanothione reductase; TROPICAL MEDICINE; Trypanocidal Agents - pharmacology; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; trypanothione reductase; Chagas disease; trypanothione reductase; tropical diseases; arylfurans
• ISSN: 1678-8060; 0074-0276; 0074-0276; 1678-8060
• DOI: 10.1590/S0074-02762006000200009

The natural lignans veraguensin and grandisin have been reported to be
active against Trypanosoma cruzi bloodstream forms. Aiming at the
total synthesis of these and related compounds, we prepared three
2-arylfurans and eight 2,5-diarylfurans. They were evaluated for their
potential as T. cruzi trypanothione reductase (TR) inhibitors as well
against the parasite's intracellular (amastigote) and bloodstream
(trypomastigote) forms. Compound 12 was the most effective against TR
with an IC50 of 48.5 μM while 7 and 14 were active against
amastigotes, inhibiting the parasite development by 60% at 20
μg/ml (59 and 90 μM, respectively). On the other hand, none
of the compounds was significantly active against the parasite
bloodstream forms even at 250 μg/ml (0.6-1.5 mM).