Protective therapy with novel chromone derivative against Leishmania donovani infection induces Th1 response in vivo.
BACKGROUND
Visceral leishmaniasis is a chronic protozoan disease caused by Leishmania donovani, an obligatory intracellular parasite that resides and multiplies within macrophages of the reticuloendothelial system. The aim of this study was to evaluate the efficacy of nine novel synthetic chromone derivatives as antileishmanial molecules in experimental murine visceral leishmaniasis.


METHODS
In vitro activity of the molecules (2, 5 and 10 μg/ml) was assessed against promastigotes of both pentavalent antimonial-responsive strain AG83 and pentavalent antimonial-resistant strain GE1F8R at days 2 (48 h), 4 (96 h) and 6 (144 h). The efficacy of the most efficient chromone derivative [C-(6-Methyl-4-oxo-4H-1-benzopyran-3-yl)-N-(p-tolyl) nitrone], designated here as NP1, was also tested against intracellular amastigotes in vitro and in vivo.


RESULTS
NP1, 5 μg/ml, inhibited the growth of AG83 and GE1F8R promastigotes by 98.57% (day 4) and 75.75% (day 6), respectively, and also inhibited the growth of intracellular amastigotes by 85% (day 3), compared to DMSO control. Treatment of L. donovani-infected mice with NP1 resulted in a 70% significant decrease in parasite load in the spleen in the 7th week after infection (5 mice in each group), with associated induction of interferon-γ synthesis by dose 2 (37.5 mg/kg body weight) compared to DMSO control. Dose 2 was found efficient over dose 1 (25 mg/kg body weight).


CONCLUSIONS
The novel synthetic chromone derivative is effective in the treatment of visceral leishmaniasis and induces the synthesis of interferon-γ in rodent models.
Cellular Immunology and Experimental Therapeutics Laboratory, Department of Zoology, West Bengal State University, Barasat, India.
Suvadip
S
Mallick
Aritri
A
Dutta
Joydip
J
Ghosh
Sourav
S
Maiti
Ajay Kumar
AK
Mandal
Rajat
R
Banerjee
Chandrakanta
C
Bandyopadhyay
Chiranjib
C
Pal
D000818:Animals; D049109:Cell Proliferation; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000276:immunology; D007893:Leishmania donovani / Q000187:drug effects* / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology*
D002867:Chromones; D007371:Interferon-gamma