TY - JOUR
T1 - Effects of trans-stilbene and terphenyl compounds on different strains of Leishmania and on cytokines production from infected macrophages
AU - Cascio, Antonio
AU - Colomba, Claudia
AU - Giacomini, Elisa
AU - Vitale, Fabrizio
AU - Bruno, Federica
AU - Castelli, Germano
AU - Roberti, Marinella
PY - 2018
Y1 - 2018
N2 - Most of the antileishmanial modern therapies are not satisfactory due to high toxicity or emergence of resistance and high cost of treatment. Previously, we observed that two compounds of a small library of trans-stilbene and terphenyl derivatives, ST18 and TR4, presented the best activity and safety profiles against Leishmania infantum promastigotes and amastigotes. In the present study we evaluated the effects of ST18 and the TR4 in 6 different species of Leishmania and the modifications induced by these two compounds in the production of 8 different cytokines from infected macrophages. We observed that TR4 was potently active in all Leishmania species tested in the study showing a leishmanicidal activity higher than that of ST18 and meglumine antimoniate in the most of the species. Moreover, TR4 was able to decrease the levels of IL-10, a cytokine able to render the host macrophage inactive allowing the persistence of parasites inside its phagolysosome, and increase the levels of IL-1β a cytokine important for host resistance to Leishmania infection by inducible iNOS-mediated production of NO, and IL-18, a cytokine implicated in the development of Th1-type immune response.
AB - Most of the antileishmanial modern therapies are not satisfactory due to high toxicity or emergence of resistance and high cost of treatment. Previously, we observed that two compounds of a small library of trans-stilbene and terphenyl derivatives, ST18 and TR4, presented the best activity and safety profiles against Leishmania infantum promastigotes and amastigotes. In the present study we evaluated the effects of ST18 and the TR4 in 6 different species of Leishmania and the modifications induced by these two compounds in the production of 8 different cytokines from infected macrophages. We observed that TR4 was potently active in all Leishmania species tested in the study showing a leishmanicidal activity higher than that of ST18 and meglumine antimoniate in the most of the species. Moreover, TR4 was able to decrease the levels of IL-10, a cytokine able to render the host macrophage inactive allowing the persistence of parasites inside its phagolysosome, and increase the levels of IL-1β a cytokine important for host resistance to Leishmania infection by inducible iNOS-mediated production of NO, and IL-18, a cytokine implicated in the development of Th1-type immune response.
KW - Cutaneous; Macrophages; Monocytes; Stilbenes; Terphenyl Compounds; U937 Cells
KW - IL-10; IL-18; IL-1β; Leishmaniasis; Stilbenes; Terphenyls; Cytokines; Humans; Inhibitory Concentration 50; Leishmania; Leishmaniasis
KW - Cutaneous; Macrophages; Monocytes; Stilbenes; Terphenyl Compounds; U937 Cells
KW - IL-10; IL-18; IL-1β; Leishmaniasis; Stilbenes; Terphenyls; Cytokines; Humans; Inhibitory Concentration 50; Leishmania; Leishmaniasis
UR - http://hdl.handle.net/10447/415850
UR - http://www.elsevier.com/inca/publications/store/6/2/2/8/2/9/index.htt
M3 - Article
VL - 184
SP - 31
EP - 38
JO - Experimental Parasitology
JF - Experimental Parasitology
SN - 0014-4894
ER -