2,3-Diketopiperazine as potential scaffold to develop new anti-Chagasic agents

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dc.contributor.authorOsorio-Nieto, Urbano
dc.contributor.authorSalas, Cristian O.
dc.contributor.authorMendez-Alvarez, Domingo
dc.contributor.authorRivera, Gildardo
dc.contributor.authorMoreno-Rodriguez, Adriana
dc.contributor.authorPerez-Cervera, Yobana
dc.contributor.authorCastillo-Real, Lizet Monserrat
dc.contributor.authorEspinosa-Bustos, Christian
dc.date.accessioned2025-01-20T20:20:01Z
dc.date.available2025-01-20T20:20:01Z
dc.date.issued2023
dc.description.abstractContinuing our program to develop compounds with potential activity against Trypanosoma cruzi, in this work we have designed and synthesized and evaluated in vitro on the trypomastigote form a new series of 2,3-diketopiperazines derivatives. By means of a two-step sequence, where one of them was a catalytic and selective C(sp(3))-H-bond reaction, nine final compounds (5a-i) were obtained. Most of these 2,3-diketopiperazines were highly active against the trypomastigote strain NINOA (LC50 < 100 mu M) compared to the reference drugs benznidazole (Bzn) and nifurtimox (Nfx). Likewise, compounds 5c and 5h showed high potency against the trypomastigote strain A1 (LC50 = 25.2 and 40.49 mu M, respectively), with 5c being four to five times more active than the reference drugs. In addition, the cytotoxicity of these compounds was determined in the murine macrophage J774 cell line, presenting in most cases, higher selectivity rates compared to Bzn and Nfx. In silico studies suggested that these 2,3-diketopiperazine derivatives could be inhibitors of the Fe-SOD enzyme at the cytosolic and mitochondrial level. Finally, these compounds would also have good oral bioavailability according to theoretical predictions.
dc.fuente.origenWOS
dc.identifier.doi10.1007/s00044-022-03003-9
dc.identifier.eissn1554-8120
dc.identifier.issn1054-2523
dc.identifier.urihttps://doi.org/10.1007/s00044-022-03003-9
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92556
dc.identifier.wosidWOS:000899712700001
dc.issue.numero1
dc.language.isoen
dc.pagina.final188
dc.pagina.inicio176
dc.revistaMedicinal chemistry research
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.title2,3-Diketopiperazine as potential scaffold to develop new anti-Chagasic agents
dc.typeartículo
dc.volumen32
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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