Conjugates of 18ß-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability.
Bioorg Med Chem
; 25(20): 5441-5451, 2017 10 15.
Article
em En
| MEDLINE
| ID: mdl-28838831
ABSTRACT
Twenty-six conjugates of 18ß-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d]imidazol-2-yl)propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI50 values of 7.80µM and 3.52µM, respectively. The enzyme inhibition ratio of nine compounds at 10µM was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Propionatos
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Neoplasias da Próstata
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Inibidores Enzimáticos
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Peptidilprolil Isomerase de Interação com NIMA
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Ácido Glicirretínico
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Imidazóis
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Antineoplásicos
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article