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
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-methy...
Gespeichert in:
Veröffentlicht in: | MedChemComm 2018-11, Vol.10 (1), p.120-127 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | 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. |
---|---|
ISSN: | 2040-2503 2040-2511 |
DOI: | 10.1039/c8md00475g |