Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni

Detalhes bibliográficos
Autor(a) principal: Di Bello, Elisabetta
Data de Publicação: 2022
Outros Autores: Noce, Beatrice, Fioravanti, Rossella, Zwergel, Clemens, Valente, Sergio, Rotili, Dante, Fianco, Giulia, Trisciuoglio, Daniela, Mourão, Marina de Moraes, Sales Junior, Policarpo Ademar, Lamotte, Suzanne, Prina, Eric, Späth, Gerald F, Häberli, Cécile, Keiser, Jennifer, Mai, Antonello
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/56618
Resumo: Department of Drug Chemistry and Technologies. Sapienza University of Rome. Rome, Italy.
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spelling Di Bello, ElisabettaNoce, BeatriceFioravanti, RossellaZwergel, ClemensValente, SergioRotili, DanteFianco, GiuliaTrisciuoglio, DanielaMourão, Marina de MoraesSales Junior, Policarpo AdemarLamotte, SuzannePrina, EricSpäth, Gerald FHäberli, CécileKeiser, JenniferMai, Antonello2023-01-25T19:08:11Z2023-01-25T19:08:11Z2022Di BELLO, Elisabetta et al. Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni. ACS Infect Dis., v. 8, n. 7, p. 1356-1366, 2022. doi: 10.1021/acsinfecdis.2c002322373-8227https://www.arca.fiocruz.br/handle/icict/56618engACS PublicationsEffects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoniinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDepartment of Drug Chemistry and Technologies. Sapienza University of Rome. Rome, Italy.Department of Drug Chemistry and Technologies. Sapienza University of Rome. Rome, Italy.Department of Drug Chemistry and Technologies. Sapienza University of Rome. Rome, Italy.Department of Drug Chemistry and Technologies. Sapienza University of Rome. Rome, Italy.Department of Drug Chemistry and Technologies. Sapienza University of Rome. Rome, Italy.Department of Drug Chemistry and Technologies. Sapienza University of Rome. Rome, Italy.Institute of Molecular Biology and Pathology. National Research Council. Rome, Italy.Institute of Molecular Biology and Pathology. National Research Council. Rome, Italy.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Institut Pasteur. Université Paris Cité. Unité de Parasitologie Moléculaire et Signalisation. Rue du Docteur Roux, Paris, France.Institut Pasteur. Université Paris Cité. Unité de Parasitologie Moléculaire et Signalisation. Rue du Docteur Roux, Paris, France.Institut Pasteur. Université Paris Cité. Unité de Parasitologie Moléculaire et Signalisation. Rue du Docteur Roux, Paris, France.Swiss Tropical and Public Health Institute. Allschwil, Switzerland/University of Basel. Basel, Switzerland.Swiss Tropical and Public Health Institute. Allschwil, Switzerland/University of Basel. Basel, Switzerland.Department of Drug Chemistry and Technologies. Sapienza University of Rome. Rome, Italy/Pasteur Institute. Cenci-Bolognetti Foundation. Sapienza University of Rome. Rome, Italy.Neglected tropical diseases (NTDs), including trypanosomiasis, leishmaniasis, and schistosomiasis, result in a significant burden in terms of morbidity and mortality worldwide every year. Current antiparasitic drugs suffer from several limitations such as toxicity, no efficacy toward all of the forms of the parasites' life cycle, and/or induction of resistance. Histone-modifying enzymes play a crucial role in parasite growth and survival; thus, the use of epigenetic drugs has been suggested as a strategy for the treatment of NTDs. We tested structurally different HDACi 1-9, chosen from our in-house library or newly synthesized, against Trypanosoma cruzi, Leishmania spp, and Schistosoma mansoni. Among them, 4 emerged as the most potent against all of the tested parasites, but it was too toxic against host cells, hampering further studies. The retinoic 2'-aminoanilide 8 was less potent than 4 in all parasitic assays, but as its toxicity is considerably lower, it could be the starting structure for further development. In T. cruzi, compound 3 exhibited a single-digit micromolar inhibition of parasite growth combined with moderate toxicity. In S. mansoni, 4's close analogs 17-20 were tested in new transformed schistosomula (NTS) and adult worms displaying high death induction against both parasite forms. Among them, 17 and 19 exhibited very low toxicity in human retinal pigment epithelial (RPE) cells, thus being promising compounds for further optimization.HDAC inhibitorsLeishmaniaS. mansoniT. cruzibenzamideshydroxamatesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/56618/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALEffects of Structurally Different HDAC Inhibitors.pdfEffects of Structurally Different HDAC Inhibitors.pdfapplication/pdf821214https://www.arca.fiocruz.br/bitstream/icict/56618/2/Effects%20of%20Structurally%20Different%20HDAC%20Inhibitors.pdfff3fa025da0bc1978cde09a01908edd9MD52icict/566182023-01-25 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dc.title.en_US.fl_str_mv Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni
title Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni
spellingShingle Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni
Di Bello, Elisabetta
HDAC inhibitors
Leishmania
S. mansoni
T. cruzi
benzamides
hydroxamates
title_short Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni
title_full Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni
title_fullStr Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni
title_full_unstemmed Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni
title_sort Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni
author Di Bello, Elisabetta
author_facet Di Bello, Elisabetta
Noce, Beatrice
Fioravanti, Rossella
Zwergel, Clemens
Valente, Sergio
Rotili, Dante
Fianco, Giulia
Trisciuoglio, Daniela
Mourão, Marina de Moraes
Sales Junior, Policarpo Ademar
Lamotte, Suzanne
Prina, Eric
Späth, Gerald F
Häberli, Cécile
Keiser, Jennifer
Mai, Antonello
author_role author
author2 Noce, Beatrice
Fioravanti, Rossella
Zwergel, Clemens
Valente, Sergio
Rotili, Dante
Fianco, Giulia
Trisciuoglio, Daniela
Mourão, Marina de Moraes
Sales Junior, Policarpo Ademar
Lamotte, Suzanne
Prina, Eric
Späth, Gerald F
Häberli, Cécile
Keiser, Jennifer
Mai, Antonello
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Di Bello, Elisabetta
Noce, Beatrice
Fioravanti, Rossella
Zwergel, Clemens
Valente, Sergio
Rotili, Dante
Fianco, Giulia
Trisciuoglio, Daniela
Mourão, Marina de Moraes
Sales Junior, Policarpo Ademar
Lamotte, Suzanne
Prina, Eric
Späth, Gerald F
Häberli, Cécile
Keiser, Jennifer
Mai, Antonello
dc.subject.en.en_US.fl_str_mv HDAC inhibitors
Leishmania
S. mansoni
T. cruzi
benzamides
hydroxamates
topic HDAC inhibitors
Leishmania
S. mansoni
T. cruzi
benzamides
hydroxamates
description Department of Drug Chemistry and Technologies. Sapienza University of Rome. Rome, Italy.
publishDate 2022
dc.date.issued.fl_str_mv 2022
dc.date.accessioned.fl_str_mv 2023-01-25T19:08:11Z
dc.date.available.fl_str_mv 2023-01-25T19:08:11Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv Di BELLO, Elisabetta et al. Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni. ACS Infect Dis., v. 8, n. 7, p. 1356-1366, 2022. doi: 10.1021/acsinfecdis.2c00232
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/56618
dc.identifier.issn.en_US.fl_str_mv 2373-8227
identifier_str_mv Di BELLO, Elisabetta et al. Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni. ACS Infect Dis., v. 8, n. 7, p. 1356-1366, 2022. doi: 10.1021/acsinfecdis.2c00232
2373-8227
url https://www.arca.fiocruz.br/handle/icict/56618
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ACS Publications
publisher.none.fl_str_mv ACS Publications
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/56618/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/56618/2/Effects%20of%20Structurally%20Different%20HDAC%20Inhibitors.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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