Medicinal Chemistry Research

, Volume 28, Issue 4, pp 395–416 | Cite as

Quinazolines as inhibitors of chromatin-associated proteins in histones

  • Frida S. Herrera-Vázquez
  • Francisco Hernández-Luis
  • José L. Medina FrancoEmail author
Review Article


It is increasing the evidence that quinazolines are inhibitors of chromatin-associated proteins in histones. Quinazolines have a broad structural diversity among the structural classes that have been designed. Herein, we review the development of selective and potent quinazolines highlighting the current state of these molecules with an emphasis on the structural requirements for the interaction within the target. Chemical synthesis and results of the biological assays in vitro or in vivo of these compounds are also discussed. There is extensive evidence that support quinazoline derivatives as inhibitors of histone methyltransferase (G9a) and G9a-like protein (GLP). There is one quinazoline analogue that inhibits an extra-terminal bromodomain motif (BET) and that is on clinical trials as potential treatment for different chronic diseases. There is also clinical evidence that quinazolines act as dual inhibitors targeting histone deacetylases (HDACs) Zn2+-dependent and kinase receptors for the potential treatment of cancer. Additional proposals of quinazoline structures are being evaluated as inhibitors targeting two or more chromatin-associated proteins simultaneously. Therefore, further improvements in synthetic methods, computational studies, and additional biological assays in vitro and in vivo remain to be addressed.


Quinazoline chromatin-associated proteins Epigenetic Histone modifiers Inhibitors 



acute myeloid leukemia


apolipoprotein A1






intrinsic clearance


deoxyribonucleic acid


half maximal effective concentration


flavin adenine dinucleotide


euchromatic histone-lysine N-methyltransferase 2


G9a-like protein


histone deacetylases


epidermal growth factor receptor


human epidermal growth factor receptor-type2


dimethylated lysine 9 histone 3


histone lysine methyltransferases


half maximal inhibitory concentration


reprogramming induced pluripotent stem cells


acetylated lysine


lysine-specific demethylase 1


monoamine oxidases


malignant brain tumor


proto-oncogenes that code for transcription factors


nicotinamide adenine dinucleotide


post-translational modification,


peroxisome proliferator-activated receptor gamma


Plasmodium histone lysine methyltransferase


vascular endothelial growth factor receptor



FSH-V acknowledges the MSc scholarship from CONACyT no. 629489. Authors are grateful to Rodrigo Aguayo-Ortiz and Jose A. Chamorro-Espino for their major contributions to prepare the figures of the manuscript. JLM-F thanks Consejo Nacional de Ciencia y Tecnologia (CONACyT) for grant 282785.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2300_MOESM1_ESM.pdf (57 kb)
Supplementary Information


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Facultad de Química, Departamento de FarmaciaUniversidad Nacional Autónoma de MéxicoMexicoMexico

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