Protective Therapy with Novel Chromone Derivative against <i>Leishmania donovani</i> Infection Induces Th1 Response in vivo

Abstract

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.

Synthesis, leishmanicidal, trypanocidal and cytotoxic activities of quinoline-chalcone and quinoline-chromone hybrids

“…The most promising of this class of compounds is licochalcone A, an oxygenated chalcone 5 isolated from the roots of the Chinese plant Glycyrrhiza spp, which inhibits the fumarate reductase, a selective target present in the mitochondria of the parasite (Chen et al, 2001). Similarly, chromones are important classes of compounds having versatile biological activities (Horton et al, 2003;Hadjeri et al, 2003;Ellis et al, 1972;Houghton et al, 2000;Mallick et al, 2011;Baloch et al, 2012). Both moieties are well known for their antiprotozoal activity.…”

“…Both moieties are well known for their antiprotozoal activity. Some synthetic chromones were effective against L. (L) donovani (Mallick et al, 2011) and L. (L) major (Baloch et al, 2012) in in vivo studies.…”

Synthesis, Leishmanicidal and Cytotoxic Activity of Triclosan-Chalcone, Triclosan-Chromone and Triclosan-Coumarin Hybrids

“…Yield 60% (1.02 mmol, 375.3 mg); pale yellow oil; IR (cm (22). Yield 82% (1.52 mmol, 450.78 mg); pale yellow oil; IR (cm (23 …”

“…Both moieties are well known for their antiprotozoal activity. Some synthetic chromones were effective against L. donovani [23] and L. major [24] in in vivo studies. Aurapten, a 7-geranyloxycoumarin, was extracted from the Rutaceae species Esenbeckia febrifuga.…”

In vivo characterization of two additional Leishmania donovani strains using the murine and hamster model

“…Bray in 1969, and the 1S strain from Sudan, first described by Stauber in 1966 , have been adapted to the in vivo situation in mice and Syrian hamsters, and have ever since become reference laboratory strains to study visceral leishmaniasis. L. donovani strains from the Indian continent, such as the DD8, AG83 and GE1F8R strains have been described in mice and hamsters . Recently, a Nepalese clinical isolate L. donovani strain (BPK282) was fully sequenced and annotated .…”