Isopentyl caffeate as a promising drug for the treatment of leishmaniasis: An in silico and in vivo study

Leishmaniasis is recognised as the second largest parasitic disease worldwide and yet a neglected disease. The current pharmacological treatments are associated with significant challenges, including high toxicity, high cost and parasitic resistance. Considering the potential of isopentyl caffeate (ICaf) as an anti-leishmanial agent, the present work evaluated the in vivo toxicity of ICaf and the absorption, distribution, metabolism, and excretion (ADME) properties in silico, aiming at the treatment of Leishmania amazonensis. For the in vivo toxicity testing, Swiss mice (Mus musculus) were treated with a single dose of ICaf. During the 14-day evaluation period, the animals underwent assessments including hippocratic screening, weight measurement, as well as histological and hematological evaluations. Analysis of ADME properties of ICaf was conducted to evaluate its pharmacokinetic characteristics and bioavailability. Characteristics, such as molar refractivity through Lipinski's Rule of Five, were identified. The in silico results showed that ICaf is considered to have good oral bioavailability and has potential to be considered as a new drug. From the in vivo toxicity testing, none of the evaluated parameters revealed toxicity of ICaf to the animals when treated intraperitoneally. The in vivo treatment reduced the lesion and the parasite load at the tested doses, corroborating the assumption that ICaf may be a potential pharmacological alternative against L. amazonensis.