کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1361334 | 981461 | 2008 | 7 صفحه PDF | دانلود رایگان |
Twenty-three heterocyclic compounds were evaluated for their potential as trypanothione reductase inhibitors. As a result, the harmaline, 10-thiaisoalloxazine, and aspidospermine frameworks were identified as the basis of inhibitors of Trypanosoma cruzi trypanothione reductase. Two new compounds showed moderately strong, linear competitive inhibition, namely N,N-dimethyl-N-[3-(7-methoxy-1-methyl-3,4-dihydro-9H-β-carbolin-9-yl)propyl]amine (15) and 1,3-bis[3-(dimethylamino)propyl]-1,5-dihydro-2H-pyrimido[4,5-b][1,4]benzothiazine-2,4(3H)-dione (21), with Ki values of 35.1 ± 3.5 μM and 26.9 ± 1.9 μM, respectively. Aspidospermine (25) inhibited T. cruzi TryR with a Ki of 64.6 ± 6.2 μM. None of the compounds inhibited glutathione reductase. Their toxicity toward promastigotes of Leishmania amazonensis was assessed.
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Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 14, 15 July 2008, Pages 6689–6695