Methyl benzoate and cinnamate analogs as modulators of DNA methylation in hepatocellular carcinoma
Por:
Castro-Vazquez D., Sánchez-Carranza J.N., Alvarez L., Juárez-Mercado K.E., Sánchez-Cruz N., Medina-Franco J.L., Antunez-Mojica M., González-Maya L.
Publicada:
1 ene 2022
Resumen:
Phenolic acids represent a large collection of phytochemical molecules present in the plant kingdom; they have an important role as epigenetic regulators, particularly as inhibitors of DNA methylation. In the present study, 14 methyl benzoate and cinnamate analogs were synthesized (11–24). Their cytotoxic activity on hepatocellular carcinoma cells (Hep3B) and immortalized human hepatocyte cells was then evaluated. In addition, its effect on the inhibition of global DNA methylation in Hep3B was also determined. Our results showed that the cinnamic derivatives 11–14 and 20–22 were more potent than the free caffeic acid (IC50 109.7–364.2 µM), being methyl 3,4-dihydroxycinammate (12) the most active with an IC50 = 109.7 ± 0.8 µM. Furthermore, 11–14, 20–23 compounds decreased overall DNA methylation levels by 63% to 97%. The analogs methyl 4-hydroxycinnamate (11), methyl 3,4,5-trimethoxycinnamate (14), methyl 4-methoxycinnamate (21), and methyl 3,4-dimethoxycinnamate (22) showed relevant activities of both cytotoxicity and global DNA methylation inhibition. The molecular docking of 21 and 14 suggested that they partly bind to the SAH-binding pocket of DNA methyltransferase 1. These results emphasize the importance of natural products and their analogs as potential sources of DNA methylation modulating agents. © 2022 John Wiley & Sons A/S.
Filiaciones:
Castro-Vazquez D.:
Centro de Investigaciones Químicas IICBA, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico
Sánchez-Carranza J.N.:
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico
Alvarez L.:
Centro de Investigaciones Químicas IICBA, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico
Juárez-Mercado K.E.:
DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autónoma de México, Mexico City, Mexico
Sánchez-Cruz N.:
DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autónoma de México, Mexico City, Mexico
Medina-Franco J.L.:
DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autónoma de México, Mexico City, Mexico
Antunez-Mojica M.:
CONACYT-Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico
González-Maya L.:
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico
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