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• W2149598224 abstract "ABSTRACT A previous screen of ∼200,000 compounds from the PubChem database identified 70 compounds possessing 50% effective concentrations (EC 50 s) below 1 μM against Leishmania major promastigotes that were not toxic to mammalian epithelial cancer cells at this concentration (E. Sharlow et al., PLoS Negl. Trop. Dis. 3:e540, 2009). Based on availability and chemical exclusion criteria, 31 of these compounds were purchased from commercial suppliers and evaluated for in vitro activity against intracellular L. donovani and L. amazonensis parasites. Benzothiazole cyanine compounds (PubChem 16196319 and 16196223) displayed potent activity against intracellular amastigotes, prompting a search for commercially available compounds that were structurally related. Pubchem 123859 (the cyanine dye thiazole orange) showed exceptionally potent activity against intracellular L. donovani in vitro (50% inhibitory concentration [IC 50 ] = 21 ± 12 nM) and low cytotoxicity against Vero cells (IC 50 = 7,800 ± 200 nM). Administration of 123859 and 16196319 at a dose of 1 mg/kg of body weight intraperitoneally (i.p.) daily for 5 days resulted in 44% ± 4% and 42% ± 3% suppression of liver parasitemia in L. donovani -infected BALB/c mice, respectively, compared to the untreated control group (the reductions in liver parasitemia were 30% ± 5% and 27% ± 4%, respectively, compared to the (2-hydroxypropyl)-β-cyclodextrin solution (HPβCD) vehicle control, which itself displayed some antileishmanial activity). Benzothiazole-containing cyanine dyes are thus potential lead compounds for the discovery of novel antileishmanial agents." @default.
• W2149598224 created "2016-06-24" @default.
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• W2149598224 date "2012-03-01" @default.
• W2149598224 modified "2023-10-16" @default.
• W2149598224 title "Identification of New Antileishmanial Leads from Hits Obtained by High-Throughput Screening" @default.
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• W2149598224 doi "https://doi.org/10.1128/aac.05412-11" @default.
• W2149598224 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3294885" @default.
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