Histone Deacetylase Inhibitors Show a Potential Leishmanicidal Effect against Leishmania braziliensis in a Mouse Infection Model and Lead to Less Toxicity than Glucantime
Year: 2025
Type: article
Abstract: 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.
Source: ACS Omega
Authors: Luciana
Ângelo de Souza, Lethícia
Kelly Ramos Andrade, Joice de Melo Agripino, Victor Hugo Ferraz da Silva, Sabrina de Oliveira Emerick, Adriana Carneiro da Silva, Larissa Coelho Pereira, Graziela Domingues
de Almeida Lima, Ingrid Rabite Garcia, Anna Cláudia
Alves Souza, Tino Heimburg, Eduardo de Almeida Marques da Silva, Leandro Licursi
de Oliveira, Luiz Otávio Guimarães Ervilha, Mariana Machado-Neves, Matheus Silva e Bastos, Raphael de Souza Vasconcellos, GustavoCosta Bressan, Abelardo Silva-Júnior, Raymond J. Pierce, Wolfgang Sippl, Juliana Lopes Rangel Fietto
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,935
Awards: G2144788382, G3690646728, G7040159013
OpenAlex ID: W4410121943