Abstract
Development of new therapeutic approach to treat leishmaniasis has become a priority. In the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. A series of β-nitrostyrenes have been synthesized by using Henry reaction and were evaluated for their antimicrobial activities by broth microdilution assay and in vitro antileishmanial activities against Leishmania donovani promastigotes by following standard guidelines. The most active compounds were futher evaluated for their in vitro antileishmanial activities against intracellular amastigotes. Among the tested β-nitrostyrenes, compounds 7, 8, 9, 12, and 17 exhibited potential activities (MICs range, 0.25–8 μg/mL) against clinically significant human pathogenic fungi. However, the microbactericidal concentrations (MBCs) and the microfungicidal concentrations (MFCs) were found to be either similar or only two-fold greater than the MICs. Anti-leishmanial results demonstrated that compounds 9, 12, 14, and 18 were found to be most active among the tested samples and exhibited 50% inhibitory concentration (IC50) by 23.40 ± 0.71, 37.83 ± 3.74, 40.50 ± 1.47, 55.66 ± 2.84 nM against L. donovani promastigotes and 30.5 ± 3.42, 21.46 ± 0.96, 26.43 ± 2.71, and 61.63 ± 8.02 nM respectively against intracellular L. donovani promastigotes amastigotes respectively which are comparable with standard AmB (19.60 ± 1.71 nM against promastigotes and 27.83 ± 3.26 nM against amastigotes). Compounds 9, 12, 14, and 18 were found to have potent in vitro leishmanicidal activity against L. donovani and found to be non-toxic against mammalian macrophages even at a concentration of 25 μM. Nitric oxide (NO) estimation studies reveals that these compounds are moderately inducing NO levels.
Highlights
Leishmaniasis is a complex infection caused by multiple species of the intracellular protozoan parasites of genus Leishmania and is transmitted by the bite of a female phlebotomine sand fly vector
The adverse effects and increasing resistance of Amphotericin B stating the need for the development of new chemical entities. In this regard we focused at the development of natural product based new anti-leishmanial agents from the known anti-fungal agents
BALB/c mice was used for the isolation of peritoneal macrophages in the ex vivo anti-amastigote study after prior approval from the Jamia Hamdard Animal Ethics Committee β-Nitrostyrenes as Anti-leishmanial Agents (JHAEC)
Summary
Leishmaniasis is a complex infection caused by multiple species of the intracellular protozoan parasites of genus Leishmania and is transmitted by the bite of a female phlebotomine sand fly vector. The disease is endemic in 82 countries of tropical and subtropical areas around the world and affects an estimated 12 million people with 2 million new cases annually (Davies et al, 2003; Murray et al, 2005; WHO, 2005, 2007a; Piscopo and Azzopardi, 2007). From the 1940s, pentavalent antimonials (Sodium antimony gluconateSAG, sodium stibogluconate-pentostam, and meglumine antimoniate-glucantime) are being used to prevent leishmaniasis since their discovery (Croft et al, 2005; Mishra et al, 2007; Santos et al, 2008) These drugs are highly toxic and require prolonged treatments with parenteral administration (Croft et al, 2005; WHO, 2010). The adverse effects and unaffordable prices of the current drugs divulge an urgent need for new, safer, effective, and cheaper alternates (Kayser et al, 2003)
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