Design and Evaluation of NSAID Derivatives as AKR1C3 Inhibitors for Breast Cancer Treatment through Computer-Aided Drug Design and In Vitro Analysis.
Molecules
; 29(8)2024 Apr 16.
Article
em En
| MEDLINE
| ID: mdl-38675620
ABSTRACT
Breast cancer is a major global health issue, causing high incidence and mortality rates as well as psychological stress for patients. Chemotherapy resistance is a common challenge, and the Aldo-keto reductase family one-member C3 enzyme is associated with resistance to anthracyclines like doxorubicin. Recent studies have identified celecoxib as a potential treatment for breast cancer. Virtual screening was conducted using a quantitative structure-activity relationship model to develop similar drugs; this involved backpropagation of artificial neural networks and structure-based virtual screening. The screening revealed that the C-6 molecule had a higher affinity for the enzyme (-11.4 kcal/mol), a lower half-maximal inhibitory concentration value (1.7 µM), and a safer toxicological profile than celecoxib. The compound C-6 was synthesized with an 82% yield, and its biological activity was evaluated. The results showed that C-6 had a more substantial cytotoxic effect on MCF-7 cells (62%) compared to DOX (63%) and celecoxib (79.5%). Additionally, C-6 had a less harmful impact on healthy L929 cells than DOX and celecoxib. These findings suggest that C-6 has promising potential as a breast cancer treatment.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Desenho de Fármacos
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Anti-Inflamatórios não Esteroides
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Membro C3 da Família 1 de alfa-Ceto Redutase
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article