Histone deacetylase inhibitors show a potential leishmanicidal effect against Leishmania braziliensis in a mouse infection model and lead to less toxicity than glucantime

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.