Literature DB >> 30378479

Aim for the Readers! Bromodomains As New Targets Against Chagas' Disease.

Victoria Lucia Alonso1, Luis Emilio Tavernelli2, Alejandro Pezza2, Pamela Cribb1,2, Carla Ritagliati2, Esteban Serra1,2.   

Abstract

Bromodomains recognize and bind acetyl-lysine residues present in histone and non-histone proteins in a specific manner. In the last decade they have raised as attractive targets for drug discovery because the miss-regulation of human bromodomains was discovered to be involved in the development of a large spectrum of diseases. However, targeting eukaryotic pathogens bromodomains continues to be almost unexplored. We and others have reported the essentiality of diverse bromodomain- containing proteins in protozoa, offering a new opportunity for the development of antiparasitic drugs, especially for Trypansoma cruzi, the causative agent of Chagas' disease. Mammalian bromodomains were classified in eight groups based on sequence similarity but parasitic bromodomains are very divergent proteins and are hard to assign them to any of these groups, suggesting that selective inhibitors can be obtained. In this review, we describe the importance of lysine acetylation and bromodomains in T. cruzi as well as the current knowledge on mammalian bromodomains. Also, we summarize the myriad of small-molecules under study to treat different pathologies and which of them have been tested in trypanosomatids and other protozoa. All the information available led us to propose that T. cruzi bromodomains should be considered as important potential targets and the search for smallmolecules to inhibit them should be empowered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

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Keywords:  Bromodomains; acetylation; bromodomain inhibitors; chagas diseases; drugzzm321990discovery; trypanosoma cruzi.

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Year:  2019        PMID: 30378479     DOI: 10.2174/0929867325666181031132007

Source DB:  PubMed          Journal:  Curr Med Chem        ISSN: 0929-8673            Impact factor:   4.530


  1 in total

Review 1.  Protein acetylation in the critical biological processes in protozoan parasites.

Authors:  Suellen Rodrigues Maran; Krista Fleck; Natália Melquie Monteiro-Teles; Tony Isebe; Pegine Walrad; Victoria Jeffers; Igor Cestari; Elton J R Vasconcelos; Nilmar Moretti
Journal:  Trends Parasitol       Date:  2021-05-12
  1 in total

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