Publicación:
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors

dc.contributor.author Galarreta B.C. es_PE
dc.contributor.author Sifuentes R. es_PE
dc.contributor.author Carrillo A.K. es_PE
dc.contributor.author Sanchez L. es_PE
dc.contributor.author Amado M.d.R.I. es_PE
dc.contributor.author Maruenda H. es_PE
dc.date.accessioned 2024-05-30T23:13:38Z
dc.date.available 2024-05-30T23:13:38Z
dc.date.issued 2008
dc.description Financial support was received from The Wellcome Trust Travel Awards 2000, 2002; TWAS 02-051; CONCYTEC: 2002-2003, 441-2004 and PUCP-DAI: 3054, 0198, 3414, and E-032.
dc.description.abstract 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-b-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 lM and 26.9 ±1.9 lM, respectively. Aspidospermine (25) inhibited T. cruzi TryR with a Ki of 64.6 ± 6.2 lM. None of the compounds inhibited glutathione reductase. Their toxicity toward promastigotes of Leishmania amazonensis was assessed. en
dc.description.sponsorship Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica - Concytec
dc.identifier.doi https://doi.org/10.1016/j.bmc.2008.05.074
dc.identifier.scopus 2-s2.0-47349130269
dc.identifier.uri https://hdl.handle.net/20.500.12390/945
dc.language.iso eng
dc.publisher Elsevier Ltd en
dc.rights info:eu-repo/semantics/openAccess
dc.subject Trypanosomatid en
dc.subject Trypanothione reductase en
dc.subject Enzymatic inhibition en
dc.title The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors
dc.type info:eu-repo/semantics/article
dspace.entity.type Publication
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