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 µM) with cell viability of 69%. Furthermore, it demonstrated anti-L. infantum action with cell viability of 13% at the highest concentration (1000 μM), while (ANF B) (16 μg/mL) demonstrated cell viability of 7%, justifying the need for further studies with n-cyclohexyl-1.2,4-oxadiazole employing experimental models of leishmaniasis.
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Acknowledgements
The authors express their gratitude to Fundação Oswaldo Cruz (FIOCRUZ) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Funding
This study was funded by Oswaldo Cruz Foundation (FIOCRUZ) (Grant VPPIS-001-FIO-18-55), Programa Institucional de Bolsas de Iniciação em Desenvolvimento Tecnológico e Inovação (PIBITI-FIOCRUZ) and the National Council for Scientific and Technological Development (CNPq) (Grants Numbers 448082/2014-4, PQ 301308/2017–9).
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CVGP conducted the experiments and YMR assisted in in vitro experiments and LLC-MK2 assay. JPVR assisted in silico experiment and revised the English language. MJT collaborated to the in vitro experiments. RNO synthesized and provided the oxadiazole molecule. WMBS and NVS guided the conduction of the article’s writing. RN concepted the idea, supervised the entire study as well as guided the students.
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Pinheiro, C.V.G., da Silva, W.M.B., Rodrigues, J.P.V. et al. Anti-Leishmania infantum in vitro effect of n-cyclohexyl-1,2,4-oxadiazole and its ADME/TOX parameters. J Parasit Dis 46, 317–322 (2022). https://doi.org/10.1007/s12639-021-01455-1
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DOI: https://doi.org/10.1007/s12639-021-01455-1