TY - JOUR
T1 - Antileishmanial activities and mechanisms of action of indole-based azoles
AU - Pagniez, Fabrice
AU - Abdala-Valencia, Hiam
AU - Marchand, Pascal
AU - Le Borgne, Marc
AU - Le Baut, Guillaume
AU - Robert-Piessard, Sylvie
AU - Le Pape, Patrice
PY - 2006/8
Y1 - 2006/8
N2 - Two 3-(α-azolylbenzyl)indoles were evaluated against Leishmania amastigotes. Both compounds proved to be very active against intracellular and axenic amastigotes. The IC50 values of the imidazole derivative, PM17, and the triazole analogue, PM19, against L. mexicana axenic amastigotes, were 4.4 ± 0.1 and 6.4 ± 0.1 μM, respectively. Against intracellular amastigotes, PM17 produced a 66% decrease of leishmanial burden at 1 μM and PM19 had an IC50 of 1.3 μM. In a Balb/c mice model of L. major leishmaniasis, administration of PM17 led to a clear-cut parasite burden reduction: 98.9% in the spleen, 79.0% in the liver and 49.9% in the popliteal node draining the cutaneous lesion. As anticipated, it was brought to the fore that PM17 decreases ergosterol biosynthesis leading to membrane fungal cell alterations. Moreover it was proved that this imidazole antifungal agent induces a parasite burden-correlated decrease in interleukine-4 production both in the splenocyte and the popliteal node of the mouse.
AB - Two 3-(α-azolylbenzyl)indoles were evaluated against Leishmania amastigotes. Both compounds proved to be very active against intracellular and axenic amastigotes. The IC50 values of the imidazole derivative, PM17, and the triazole analogue, PM19, against L. mexicana axenic amastigotes, were 4.4 ± 0.1 and 6.4 ± 0.1 μM, respectively. Against intracellular amastigotes, PM17 produced a 66% decrease of leishmanial burden at 1 μM and PM19 had an IC50 of 1.3 μM. In a Balb/c mice model of L. major leishmaniasis, administration of PM17 led to a clear-cut parasite burden reduction: 98.9% in the spleen, 79.0% in the liver and 49.9% in the popliteal node draining the cutaneous lesion. As anticipated, it was brought to the fore that PM17 decreases ergosterol biosynthesis leading to membrane fungal cell alterations. Moreover it was proved that this imidazole antifungal agent induces a parasite burden-correlated decrease in interleukine-4 production both in the splenocyte and the popliteal node of the mouse.
KW - Antileishmanials
KW - Azole derivatives
KW - Ergosterol
KW - Interleukine-4
KW - Leishmania
UR - http://www.scopus.com/inward/record.url?scp=33746174190&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746174190&partnerID=8YFLogxK
U2 - 10.1080/14756360600700517
DO - 10.1080/14756360600700517
M3 - Article
C2 - 16918075
AN - SCOPUS:33746174190
SN - 1475-6366
VL - 21
SP - 277
EP - 283
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 3
ER -