Synthesis, biological evaluation and molecular docking of 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs containing the piperazine moiety.
Bioorg Med Chem
; 27(20): 115081, 2019 10 15.
Article
en En
| MEDLINE
| ID: mdl-31493989
ABSTRACT
Prostate cancer (PCa) is a major cause of cancer-related male death in worldwide. To develop of potential anti-prostate cancer agents, 22 kinds of 4-Amino-2H-benzo[h]chromen-2-one analogs were designed and synthesized as potent androgen receptor (AR) antagonist through rational drug modification leading to the discovery of a series of novel antiproliferative compounds. Analogs (3, 4, 5, 7, 8, 10, 11, 12, 16, 18, 21, 23, and 24) exhibited potent antagonistic potency against AR (inhibition >50%), and exhibited potent AR binding affinities as well as displayed the higher activities than finasteride toward LNCaP cells (AR-rich) versus PC-3 cells (AR-deficient). Moreover, the docking study suggested that the most potent antagonist 23 mainly bind to AR ligand binding pocket (LBP) site through Van der Waals' force interactions. The structure-activity relationship (SAR) of these designed 4-Amino-2H-benzo[h]chromen-2-one analogs was rationally explored and discussed. Collectively, this work provides a potential lead compound for anticancer agent development related to prostate cancer therapy, and took a step forward towards the development of novel and improved AR antagonists.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Receptores Androgénicos
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Antagonistas de Receptores Androgénicos
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Simulación del Acoplamiento Molecular
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Piperazina
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Antineoplásicos
Límite:
Humans
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Male
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China