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Targeting HDACs of apicomplexans: structural insights for a better treatment

Published online by Cambridge University Press:  31 March 2022

Caroline de Moraes de Siqueira ,
Mariana Sayuri Ishikawa Fragoso ,
Vanessa Rossini Severo ,
Isis Venturi Biembengut ,
Sheila Cristina Nardelli  and
Tatiana de Arruda Campos Brasil de Souza Open the ORCID record for Tatiana de Arruda Campos Brasil de Souza [Opens in a new window]
Caroline de Moraes de Siqueira
Affiliation:
Instituto Carlos Chagas – Fundação Oswaldo Cruz – Fiocruz/PR, Curitiba, PR, Brazil
Mariana Sayuri Ishikawa Fragoso
Affiliation:
Instituto Carlos Chagas – Fundação Oswaldo Cruz – Fiocruz/PR, Curitiba, PR, Brazil
Vanessa Rossini Severo
Affiliation:
Instituto Carlos Chagas – Fundação Oswaldo Cruz – Fiocruz/PR, Curitiba, PR, Brazil
Isis Venturi Biembengut
Affiliation:
Instituto Carlos Chagas – Fundação Oswaldo Cruz – Fiocruz/PR, Curitiba, PR, Brazil
Sheila Cristina Nardelli
Affiliation:
Instituto Carlos Chagas – Fundação Oswaldo Cruz – Fiocruz/PR, Curitiba, PR, Brazil
Tatiana de Arruda Campos Brasil de Souza*
Affiliation:
Instituto Carlos Chagas – Fundação Oswaldo Cruz – Fiocruz/PR, Curitiba, PR, Brazil
*
Author for correspondence: Tatiana de Arruda Campos Brasil de Souza, E-mail: [email protected]
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Abstract

Aetiologic agents of diseases such as malaria and toxoplasmosis are found in representatives of the phylum Apicomplexa. Therefore, apicomplexan parasites are known to have a significant impact on public health. Epigenetic factors such as histone acetylation/deacetylation are among the main mechanisms of gene regulation in these parasites. Histone deacetylases (HDACs) have aroused a great deal of interest over the past 20 years for being promising targets in the development of drugs for treating several diseases such as cancer. In addition, they have also been shown to be effective for parasitic diseases. However, little is known about the structure of these proteins, as well as their interactions with specific ligands. In this paper, we modelled 14 HDACs from different apicomplexan parasites and performed molecular docking with 12 ligands analogous to the HDAC inhibitors FR235222 and apicidin, which had previously been tested against Toxoplasma gondii and Plasmodium falciparum. In this in silico study, we were able to gather relevant structural data regarding these proteins as well as insights into protein–ligand interactions for testing and developing drugs for these diseases.

Keywords

ApicidinApicomplexaHDAC inhibitorHDACshomology modellingmolecular docking
Type
Research Article
Information
Parasitology , Volume 149 , Issue 7 , June 2022 , pp. 956 - 967
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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