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In vitro evaluation and in vivo efficacy of nitroimidazole-sulfanyl ethyl derivatives against Leishmania (V.) braziliensis and Leishmania (L.) mexicana

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Abstract

The aim of this study was to synthesize several small molecules of the type 5-nitroimidazole-sulfanyl and evaluate biological properties against the main Leishmania species that cause cutaneous leishmaniasis in Venezuela. Final compounds 4–7 were generated through simple nucleophilic substitution of 1-(2-chloroethyl)-2-methyl-5-nitroimidazole 3 with 2-mercaptoethanol, 1-methyl-2-mercaptoethanol, and 2-thyolacetic acid derivative. Compound 8 was synthesized via a coupling reaction between 7 and (S)-Methyl 2-amino-4-methylpentanoate hydrochloride. The inhibitory concentrations of (3, 4, 7, 8) against Leishmania (L.) mexicana and (V.) braziliensis in promastigotes and experimentally infected macrophages were determined by in vitro activity assays. Compounds 7 and 8 shown high activity against both species of Leishmania and were selected for the in vivo evaluation. Animals were infected with promastigotes of the two species and divided into four groups of ten (10) animals and a control group. Intralesional injection way was used for the treatment. The parasitological diagnostic after treatment was obtained by PCR using species specific oligonucleotides. The two Leishmania species were susceptible to compounds 7 and 8 in vivo assays. The results indicated that both compounds reduce significantly (96%) the size of the lesion and cure 63% of the mice infected with L (L) mexicana or L (V) braziliensis as was determined by PCR. The results are indicating that both compounds may represent an alternative treatment for these two Leishmania species.

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Acknowledgements

We thank the Instituto de Investigaciones Farmacéuticas (IIF) and Consejo de Desarrollo Científico y Humanístico de la Universidad Central de Venezuela (CDCH-UCV, PG. 09-8819-2013/2).

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Authors and Affiliations

  1. Organic Synthesis Laboratory, Faculty of Pharmacy, Central University of Venezuela, Los Chaguaramos 1041-A, Caracas, 47206, Venezuela

    Zuleima Blanco, Hegira Ramírez & Jaime E. Charris

  2. Biotechnology Unit, Faculty of Pharmacy, Central University of Venezuela, Los Chaguaramos 1041-A, Caracas, 47206, Venezuela

    Michael R. Mijares

  3. Facultad de Medicina, Universidad de Las Américas, Quito, Ecuador

    Hegira Ramírez

  4. Escuela de Medicina, Universidad Espíritu Santo, Samborondón, Ecuador

    Esteban Fernandez-Moreira

  5. Institute of Biomedicine, Faculty of Medicine, Central University of Venezuela, 1010-A, 4043, Caracas, Venezuela

    Henry J. Oviedo & Noris M. Rodríguez

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  1. Zuleima Blanco
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Correspondence to Jaime E. Charris.

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Supplementary file1 (DOCX 3220 KB)

436_2021_7266_MOESM2_ESM.docx

Supplementary file2 Supplementary data of NMR spectra (1H and 13C NMR) for all compounds described and some Tables are available. (DOCX 40.5 KB)

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Blanco, Z., Mijares, M.R., Ramírez, H. et al. In vitro evaluation and in vivo efficacy of nitroimidazole-sulfanyl ethyl derivatives against Leishmania (V.) braziliensis and Leishmania (L.) mexicana. Parasitol Res 120, 3307–3317 (2021). https://doi.org/10.1007/s00436-021-07266-w

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