Design, Synthesis and Cytotoxicity Evaluation of Novel Indole Derivatives Containing Benzoic Acid Group as Potential AKR1C3 Inhibitors.
Chem Biodivers
; 17(12): e2000519, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-33111427
ABSTRACT
Castration-resistant prostate cancer (CRPC) is a fatal, metastatic form of prostate cancer, characterized by reactivation of the androgen axis. Aldo-keto reductase 1C3 (AKR1C3) converts androstenedione (AD) and 5α-androstanedione to testosterone (T) and 5α-dihydrotestosterone (DHT), respectively. In CRPC, AKR1C3 is upregulated and implicated in drug resistance and has been regarded as a potential therapeutic target. Here we examined a series of indole derivatives containing benzoic acid or phenylhydroxamic acid and found that 4-({3-[(3,4,5-trimethoxyphenyl)sulfanyl]-1H-indol-1-yl}methyl)benzoic acid (3e) and N-hydroxy-4-({3-[(3,4,5-trimethoxyphenyl)sulfanyl]-1H-indol-1-yl}methyl)benzamide (3q) inhibited 22Rv1â
cell proliferation with IC50 values of 6.37â
µM and 2.72â
µM, respectively. In enzymatic assay, compounds 3e and 3q exhibited potent inhibitory effect against AKR1C3 (IC50 =0.26 and 2.39â
µM, respectively). These results indicated that compounds 3e and 3q might be useful leads for further investigation of more potential AKR1C3 inhibitors used for CRPC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Benzoatos
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Desenho de Fármacos
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Inibidores Enzimáticos
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Neoplasias de Próstata Resistentes à Castração
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Membro C3 da Família 1 de alfa-Ceto Redutase
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Indóis
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Antineoplásicos
Limite:
Humans
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Male
Idioma:
En
Revista:
Chem Biodivers
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article