Jump to main content
Jump to site search


Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds

Abstract

A series of novel indazole-pyrone hybrids were synthesized by one pot reaction between N-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2H-pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were obtained with good to excellent yields (72–92%) and characterized by NMR and single crystal X-ray diffraction. Nineteen compounds were tested in vitro against both Leishmania donovani (MHOM/ET/67/HU3, also called LV9) axenic and intramacrophage amastigotes. Among all, five compounds showed anti-leishmanial activity against intracellular L. donovani with IC50 in the range of 2.25 to 62.56 µM. 3-(1-(3-Chloro-2-ethyl-2H-indazol-6-ylamino)ethylidene)-6-methyl-3H-pyran-2,4-dione 6f was found to be the most active compound on axenic amastigotes and intramacrophage amastigotes of L. donovani with an IC50 values of 2.48 ± 1.02 μM and 2.25 ± 1.89 μM, respectively. However, cytotoxicity of the most promising compounds justifies further pharmacomodulations.

Back to tab navigation

Supplementary files

Publication details

The article was received on 24 Sep 2018, accepted on 15 Nov 2018 and first published on 19 Nov 2018


Article type: Research Article
DOI: 10.1039/C8MD00475G
Citation: Med. Chem. Commun., 2018, Accepted Manuscript
  •   Request permissions

    Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds

    E. M. Rakib, M. Baltas, P. M. Loiseau, L. Bouissane, S. Mojahidi, M. Berkani, A. Allam, S. Cojean, M. El Ghozlani and C. Menendez, Med. Chem. Commun., 2018, Accepted Manuscript , DOI: 10.1039/C8MD00475G

Search articles by author

Spotlight

Advertisements