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2021, Número 1

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TIP Rev Esp Cienc Quim Biol 2021; 24 (1)


Evaluación biológica in vitro e in silico de derivados de ftalamida como agentes antiproliferativos

Sierra-Rivera CA, Kashif M, Vázquez-Jiménez LK, Zugasti-Cruz A, Juárez-Saldivar A, Paz-González AD, Rivera G
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Idioma: Ingles.
Referencias bibliográficas: 35
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Archivo PDF: 985.86 Kb.


PALABRAS CLAVE

antiproliferativo, metiltransferasa 1 de ADN, acoplamiento molecular, ftalimida.

RESUMEN

La estructura de la ftalimida es considerada un bloque de construcción para el desarrollo de nuevos agentes anticancerígenos. En este trabajo, se evaluó la actividad antiproliferativa de cuarenta y tres derivados de ftalimida contra las líneas celulares cancerígenas de cérvix (HeLa), hígado (HepG2), mama (4T1), y la línea celular normal de fibroblastos murinos (3T3). Por último, se realizó un análisis de acoplamiento molecular de los derivados de la ftalimida en el sitio activo de la enzima metiltransferasa 1 de DNA (DNMT1, por sus siglas en inglés) y el receptor del factor de crecimiento endotelial vascular 2 (VEGR2, por sus siglas en inglés) como posibles blancos farmacológicos. Los compuestos C16, E11 y E16 mostraron la mejor actividad antiproliferativa contra las líneas celulares HeLa y 4T1. Solamente, el compuesto H16 disminuyó 32% la proliferación celular de la línea HepG2. Los compuestos H5, H16, E2, E16 y C1 no afectaron la proliferación celular de la línea 3T3. El análisis de acoplamiento molecular demostró que los derivados de la ftalimida tienen una mayor afinidad que la S-adenosil-l-homocisteína, un potente inhibidor de la metiltransferasa 1 de DNA. Sin embargo, los resultados del acoplamiento molecular no se correlacionan con los efectos antiproliferativos; lo cual sugiere que los compuestos activos tienen otro mecanismo de acción.


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