TY - JOUR
T1 - Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes
AU - Haavikko, Raisa
AU - Nasereddin, Abedelmajeed
AU - Sacerdoti-Sierra, Nina
AU - Kopelyanskiy, Dmitry
AU - Alakurtti, Sami
AU - Tikka, Mari
AU - Jaffe, Charles L.
AU - Yli-Kauhaluoma, Jari
PY - 2014
Y1 - 2014
N2 - The synthesis of heterocyclic betulin derivatives and
their activity against Leishmania donovani is reported.
Betulonic acid was used as a versatile intermediate.
Several different fused heterocycles were introduced at
the 2,3-position of the lupane skeleton including
isoxazole, pyrazine, pyridine, indole and pyrazole rings.
Also the 28-position was modified. Three compounds, 5, 8
and 25, showed low micromolar activity with IC50 values
of 13.2, 4.3 and 7.2 µM, respectively. Compound 8 showed
the best activity and selectivity, and its activity was
tested on infected macrophages using a concentration, 5
µM, where no macrophage toxicity was exhibited.
Interestingly, the activity of compound 8 on axenic
amastigotes and Leishmania-infected macrophages was
similar
AB - The synthesis of heterocyclic betulin derivatives and
their activity against Leishmania donovani is reported.
Betulonic acid was used as a versatile intermediate.
Several different fused heterocycles were introduced at
the 2,3-position of the lupane skeleton including
isoxazole, pyrazine, pyridine, indole and pyrazole rings.
Also the 28-position was modified. Three compounds, 5, 8
and 25, showed low micromolar activity with IC50 values
of 13.2, 4.3 and 7.2 µM, respectively. Compound 8 showed
the best activity and selectivity, and its activity was
tested on infected macrophages using a concentration, 5
µM, where no macrophage toxicity was exhibited.
Interestingly, the activity of compound 8 on axenic
amastigotes and Leishmania-infected macrophages was
similar
U2 - 10.1039/c3md00282a
DO - 10.1039/c3md00282a
M3 - Article
SN - 2040-2503
VL - 5
SP - 445
EP - 451
JO - MedChemComm
JF - MedChemComm
IS - 4
ER -