Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8md00475g

• Published in: MedChemComm Vol. 10; no. 1; pp. 120 - 127
• Main Authors: El Ghozlani, M., Bouissane, L., Berkani, M., Mojahidi, S., Allam, A., Menendez, C., Cojean, S., Loiseau, P. M., Baltas, M., Rakib, E. M.
• Format: Journal Article
• Language: English
• Published: Royal Society of Chemistry 19-11-2018
• Subjects: Chemistry
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c8md00475g

A series of novel indazole–pyrone hybrids are synthesized and tested
in vitro
against both
Leishmania donovani
axenic and intramacrophage amastigotes.
A series of novel indazole–pyrone hybrids were synthesized by a one pot reaction between
N
-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2
H
-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 in 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 an IC
50
in the range of 2.25 to 62.56 μM. 3-(1-(3-Chloro-2-ethyl-2
H
-indazol-6-ylamino)ethylidene)-6-methyl-3
H
-pyran-2,4-dione
6f
was found to be the most active compound for axenic amastigotes and intramacrophage amastigotes of
L. donovani
with IC
50
values of 2.48 ± 1.02 μM and 2.25 ± 1.89 μM, respectively. However, the cytotoxicity of the most promising compound justifies further pharmacomodulations.