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

A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between -alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2 -pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were o...

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Bibliographic Details
Published in:MedChemComm 2019-01, Vol.10 (1), p.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: Article
Language:English
Subjects:
Acetic acid
Amastigotes
Chemical Sciences
Chemical synthesis
Cytotoxicity
Diketones
Hybrids
Indium
Leishmania donovani
NMR
Nuclear magnetic resonance
Pharmacology
Single crystals
Stannous chloride
Tetrahydrofuran
Toxicity
X-ray diffraction
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Summary:A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between -alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2 -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 against both (MHOM/ET/67/HU3, also called LV9) axenic and intramacrophage amastigotes. Among all, five compounds showed anti-leishmanial activity against intracellular with an IC in the range of 2.25 to 62.56 μM. 3-(1-(3-Chloro-2-ethyl-2 -indazol-6-ylamino)ethylidene)-6-methyl-3 -pyran-2,4-dione was found to be the most active compound for axenic amastigotes and intramacrophage amastigotes of with IC 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.
ISSN:2040-2503
2040-2511
2040-2511
DOI:10.1039/C8MD00475G