Design and development of novel inhibitors of aldo-ketoreductase 1C1 as potential lead molecules in treatment of breast cancer.
Mol Cell Biochem
; 476(8): 2975-2987, 2021 Aug.
Article
en En
| MEDLINE
| ID: mdl-33770316
ABSTRACT
Aldo-keto reductase 1C1 (AKR1C1) is a hydroxysteroid dehydrogenase, known to inactivate the biologically active progesterone into its corresponding 20 α-hydroxyprogesterone. Increased expression of the AKR1C1 gene in oncogenesis is linked with resistance to various anticancer agents and hence it is considered as an emerging drug target for the design and developing the novel anticancer drugs. We have performed QSAR pharmacophore modeling for AKR1C1 inhibitors followed by a virtual screening of ~ 59,000 compounds present at the Maybridge database. The screened compounds were refined using drug-like filters of Lipinski rule, ADMET plot, molecular docking and scoring and subsequently top 20 hits were selected. Selected compounds were subjected to the in vitro for AKR1C1 inhibition assay and best seven compounds bearing excellent binding affinity to the AKR1C1 were finally selected. The identified compounds may be exploited in hit-to-lead development and may also prove as an interventional strategy in preventing a pre-term birth due to declining levels of progesterone.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Diseño de Fármacos
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Inhibidores Enzimáticos
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Descubrimiento de Drogas
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Ensayos Analíticos de Alto Rendimiento
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20-Hidroxiesteroide Deshidrogenasas
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Mol Cell Biochem
Año:
2021
Tipo del documento:
Article
País de afiliación:
India