Histone Deacetylase Inhibitors Show a Potential Leishmanicidal Effect against <i>Leishmania braziliensis</i> in a Mouse Infection Model and Lead to Less Toxicity than Glucantime
Leishmania braziliensis is the primary cause of cutaneous leishmaniasis (CL) in the New World. Current treatments have significant limitations, including severe side effects and parasite resistance. Histone deacetylases (HDAC) are critical regulators of chromatin structure and represent potential drug targets for leishmaniasis. This study evaluated three HDAC inhibitors (HDACi), TH60, TH74, and TH85, in BALB/c mice infected with L. braziliensis, comparing their efficacy to the standard treatment, glucantime. Two doses were tested, and lesion size, parasite load, kidney and liver enzyme levels, and histopathological analyses were carried out. HDACi effectively reduced lesion size and parasite presence, with lower toxicity and fewer organ alterations than glucantime. Among the tested compounds, TH60 was the best-tested HDACi. These findings highlight the potential application of the tested HDACi as leishmanicidal agents against L. braziliensis, positioning them as promising candidates for developing new drugs targeting cutaneous leishmaniasis.
Authors
- Luı́s Moniz Pereira (ORCID: https://orcid.org/0000-0001-7880-4322)
- Raphael de Souza Vasconcellos (ORCID: https://orcid.org/0000-0002-5064-052X)
- Graziela Domingues de Almeida Lima (ORCID: https://orcid.org/0000-0001-5954-3606)
- Tino Heimburg
- Wolfgang Sippl (ORCID: https://orcid.org/0000-0002-5985-9261)
- Victor Hugo Ferraz da Silva (ORCID: https://orcid.org/0000-0001-9344-1777)
- Ingrid Rabite Garcia (ORCID: https://orcid.org/0000-0001-7814-132X)
- Eduardo de Almeida Marques da Silva (ORCID: https://orcid.org/0000-0003-4015-5915)
- Joice de Melo Agripino (ORCID: https://orcid.org/0000-0002-1225-6420)
- Raymond J. Pierce (ORCID: https://orcid.org/0000-0001-9820-8608)
- Luciana Ângelo de Souza (ORCID: https://orcid.org/0000-0002-7847-3022)
- Luiz Otávio Guimarães‐Ervilha (ORCID: https://orcid.org/0000-0001-6355-2492)
- Gustavo Costa Bressan (ORCID: https://orcid.org/0000-0002-9741-4554)
- Juliana Lopes Rangel Fietto (ORCID: https://orcid.org/0000-0001-6122-1710)
- Mariana Machado‐Neves (ORCID: https://orcid.org/0000-0002-7416-3529)
- Sabrina de Oliveira Emerick (ORCID: https://orcid.org/0000-0002-4620-5154)
- Adriana Carneiro da Silva
- Leandro Licursi de Oliveira (ORCID: https://orcid.org/0000-0003-4353-7011)
- Anna Cláudia Alves de Souza (ORCID: https://orcid.org/0000-0002-7341-2642)
- Matheus Silva e Bastos (ORCID: https://orcid.org/0000-0002-1834-6005)
- Abelardo Silva-Júnior
- Leandro Oliveira de Andrade (ORCID: https://orcid.org/0009-0007-0025-7198)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Universidade Federal de Viçosa (BR)
- Inserm (FR)
- Université de Lille (FR)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Center for Infection and Immunity of Lille (FR)
- Martin Luther University Halle-Wittenberg (DE)
Publication Details
- Journal
- ACS Omega
- Published
- 2025-05-06
- DOI
- https://doi.org/10.1021/acsomega.4c11381
- Citations
- 3
- Primary Topic
- Research on Leishmaniasis Studies
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais
- Seventh Framework Programme