Anti-Leishmania infantum in vitro effect of n-cyclohexyl-1,2,4-oxadiazole and its ADME/TOX parameters

Abstract

Leishmaniasis is a disease that represents a serious global health problem with a potentially fatal outcome in some cases. Leishmania spp. is transmitted by the bite of a sandfly and the disease is endemic in 98 countries. Treatment is carried out with toxic drugs and not consistently effective, so there is a need for new treatments. Oxadiazoles are five-membered heterocyclic compounds, and their antileishmanial activity is well documented in the literature. Specifically, n-cyclohexyl-1,2,4-oxadiazole (2b) was designed to obtain the simplified molecular data line entry system (SMILES). The approach for predicting pharmacokinetic properties used was pkCSM-Pharmacokinetics and ADME/TOX parameters were achieved. SMILES of 2b and Amphotericin B (ANF B) were submitted to the server and the results were compared. The cytotoxic action of 2b on host cells (LLC-MK2) was also evaluated, using MTT salt and antileishmanial activity against Leishmania infantum promastigotes at different concentrations for 24 h. The molecule 2b studied here demonstrated low toxicity in LLC-MK2 cells even at the highest concentration (1000 lM) with cell viability of 69%. Furthermore, it demonstrated anti-L. infantum action with cell viability of 13% at the highest concentration (1000 lM), while (ANF B) (16 lg/mL) demonstrated cell viability of 7%, justifying the need for further studies with n-cyclohexyl-1.2,4-oxadiazole employing experimental models of leishmaniasis.

Leishmanicidal and healing effects of 3β,6β,16β-trihydroxy lup-20 (29)-ene isolated from Combretum leprosum on Leishmania braziliensis infection in vitro and in vivo

“…Promastigotes were distributed in 48-well plates in a volume of 160 μL in each well and diluted CLF-1 was added at the respective concentrations of 5, 10, 25, 50 and 100 μg/mL. For control, 1% DMSO, Amphotericin B (16 μg/mL) and non-supplemented Schneider medium were used [19]. The plates were incubated for 24 and 48 hours at 25˚C and the number of viable promastigotes was determined.…”