New Coumarin Derivatives as Anti-Breast and Anti-Cervical Cancer Agents Targeting VEGFR-2 and p38α MAPK.
Arch Pharm (Weinheim)
; 350(9)2017 Sep.
Article
en En
| MEDLINE
| ID: mdl-28787092
ABSTRACT
Breast and cervical cancers are the most common gender-specific cancers affecting women worldwide. In this investigation, we highlighted the synthesis, VEGFR-2 and p38α MAPK inhibitory activity of new series of fluorinated coumarin-based derivatives featuring a variety of bioactive chemical moieties attached or fused to the coumarin nucleus at the 3 and/or 4 position. The bioactive inhibitors were further assessed for their anti-proliferative effect against human MCF-7 breast cancer and HeLa cervical cancer cell lines, respectively. Most of the tested compounds showed potent preferential inhibition effects against human VEGFR-2 and remarkable anticancer activities in the human breast cancer cell line MCF-7. Compounds 29, 24, and 2 displayed the highest inhibitory activity against VEGFR-2 (94% inhibition) and they were the most potent anticancer agents toward MCF-7 cancer cells with IC50 values of 7.90, 8.28, and 8.30 µg/mL, respectively. Compound 13 inhibited p38α MAPK phosphorylation with a significant reduction in % cell viability against HeLa cancer cells at 10 and 30 µM. Docking experiments carried out on VEGFR-2 and p38 MAPK crystallographic structures revealed that the active compounds bind to the active sites through H-bonds, arene-cation, and hydrophobic π-π interactions. QSAR analysis demonstrated considerable correlation coefficient (R2 = 0.76969) and root mean square error (RMSE = 0.10446) values. Also, the residual values between the experimental pIC50 and predicted pIC50 are very close, indicating the reliability of the established QSAR model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Neoplasias del Cuello Uterino
/
Cumarinas
/
Receptor 2 de Factores de Crecimiento Endotelial Vascular
/
Proteínas Quinasas p38 Activadas por Mitógenos
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Año:
2017
Tipo del documento:
Article
País de afiliación:
Egipto