Design, synthesis, and biological evaluation of 3-(1-benzotriazole)-nor-ß-lapachones as NQO1-directed antitumor agents.
Bioorg Chem
; 113: 104995, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34034133
ABSTRACT
A series of novel 3-(1-benzotriazole)-nor-ß-lapachones 5a-5l were synthesized as the NQO1-targeted anticancer agents. Most of these compounds displayed good antiproliferative activity against the breast cancer MCF-7, lung cancer A549 and hepatocellular carcinoma HepG2 cells in agreements with their NQO1 activity. Among them, compound 5k was identified as a favorable NQO1 substrate. It could activate the ROS production in a NQO1-dependent manner, arrest tumor cell cycle at G0/G1 phase, promote tumor cell apoptosis, and decrease the mitochondrial membrane potential. In HepG2 xenograft models, 5k significantly suppressed the tumor growth with no influences on animal body weights. Therefore, 5k could be a good lead for further anticancer drug developments.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Triazóis
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Benzofuranos
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Desenho de Fármacos
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Naftoquinonas
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NAD(P)H Desidrogenase (Quinona)
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Inibidores Enzimáticos
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2021
Tipo de documento:
Article