Identification of cytotoxic, glutathione-reactive moieties inducing accumulation of reactive oxygen species via glutathione depletion.
Bioorg Med Chem
; 26(8): 1453-1461, 2018 05 01.
Article
em En
| MEDLINE
| ID: mdl-29170028
ABSTRACT
Reactive oxygen species (ROS) play an essential role in the survival and progression of cancer. Moderate oxidative stress drives proliferation, whereas high levels of ROS induce cytotoxicity. Compared to cancer cells, healthy cells often exhibit lower levels of oxidative stress. Elevation of cellular ROS levels by small molecules could therefore induce cancer-specific cytotoxicity. We have employed high-throughput phenotypic screening to identify inducers of ROS accumulation. We found 4,5-dihalo-2-methylpyridazin-3-one (DHMP) and 2,3,4,5(6)-tetrachloro-6(5)-methylpyridine (TCMP) moieties to strongly deplete GSH, to cause ROS accumulation and to induce cell death. Small molecules containing these fragments will most likely share the same properties and should therefore be carefully considered in the development of bioactive molecules.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
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Glutationa
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article