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- W2059643240 abstract "The natural curcuminoids curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) have been chemically modified to give 46 analogs and 8 pairs of 1:1 mixture of curcuminoid analogs and these parent curcuminoids and their analogs were assessed against protozoa of the Trypanosoma and Leishmania species. The parent curcuminoids exhibited low antitrypanosomal activity (EC50 for our drug-sensitive Trypanosoma brucei brucei line (WT) of compounds 1, 2 and 3 are 2.5, 4.6 and 7.7 μM, respectively). Among 43 curcuminoid analogs and 8 pairs of 1:1 mixture of curcuminoid analogs tested, 8 pure analogs and 5 isomeric mixtures of analogs exhibited high antitrypanosomal activity in submicromolar order of magnitude. Among these highly active analogs, 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one (40) was the most active compound, with an EC50 value of 0.053 ± 0.007 μM; it was about 2-fold more active than the standard veterinary drug diminazene aceturate (EC50 0.12 ± 0.01 μM). Using a previously characterized diminazene-resistant T. b. brucei (TbAT1-KO) and a derived multi-drug resistant line (B48), no cross-resistance of curcuminoids was observed to the diamidine and melaminophenyl arsenical drugs that are the current treatments. Indeed, curcuminoids carrying a conjugated keto (enone) motif, including 40, were significantly more active against T. b. brucei B48. This enone motif was found to contribute to particularly high trypanocidal activity against all Trypanosoma species and strains tested. The parent curcuminoids showed low antileishmanial activity (EC50 values of compounds 1 and 2 for Leishmania mexicana amastigotes are 16 ± 3 and 37 ± 6 μM, respectively) while the control drug, pentamidine, displayed an EC50 of 16 ± 2 μM. Among the active curcuminoid analogs, four compounds exhibited EC50 values of less than 5 μM against Leishmania major promastigotes and four against L. mexicana amastigotes. No significant difference in sensitivity to curcuminoids between L. major promastigotes and L. mexicana amastigotes was observed. The parent curcuminoids and most of their analogs were also tested for their toxicity against human embryonic kidney (HEK) cells. All the curcuminoids exhibited lower toxicity to HEK cells than to T. b. brucei bloodstream forms and only one of the tested compounds showed significantly higher activity against HEK cells than curcumin (1). The selectivity index for T. b. brucei ranged from 3-fold to 1500-fold. The selectivity index for the most active analog, the enone 40, was 453-fold." @default.
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- W2059643240 date "2010-03-01" @default.
- W2059643240 modified "2023-10-10" @default.
- W2059643240 title "Curcuminoid analogs with potent activity against Trypanosoma and Leishmania species" @default.
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- W2059643240 cites W1963648801 @default.
- W2059643240 cites W1964012968 @default.
- W2059643240 cites W1964951360 @default.
- W2059643240 cites W1971781743 @default.
- W2059643240 cites W1979094234 @default.
- W2059643240 cites W1984430274 @default.
- W2059643240 cites W1984626136 @default.
- W2059643240 cites W1985049657 @default.
- W2059643240 cites W1985111667 @default.
- W2059643240 cites W1988608720 @default.
- W2059643240 cites W1989178699 @default.
- W2059643240 cites W1991098746 @default.
- W2059643240 cites W1991327193 @default.
- W2059643240 cites W1992116796 @default.
- W2059643240 cites W1992537760 @default.
- W2059643240 cites W1994661314 @default.
- W2059643240 cites W1996017124 @default.
- W2059643240 cites W1997583737 @default.
- W2059643240 cites W1998813367 @default.
- W2059643240 cites W2004342153 @default.
- W2059643240 cites W2006620922 @default.
- W2059643240 cites W2014735022 @default.
- W2059643240 cites W2017622972 @default.
- W2059643240 cites W2020278122 @default.
- W2059643240 cites W2020601622 @default.
- W2059643240 cites W2026488701 @default.
- W2059643240 cites W2026965104 @default.
- W2059643240 cites W2033431239 @default.
- W2059643240 cites W2034490413 @default.
- W2059643240 cites W2039703634 @default.
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- W2059643240 cites W2044425129 @default.
- W2059643240 cites W2051788892 @default.
- W2059643240 cites W2052489898 @default.
- W2059643240 cites W2055625001 @default.
- W2059643240 cites W2060592209 @default.
- W2059643240 cites W2084889403 @default.
- W2059643240 cites W2088803890 @default.
- W2059643240 cites W2098430714 @default.
- W2059643240 cites W2099155653 @default.
- W2059643240 cites W2100736039 @default.
- W2059643240 cites W2101740195 @default.
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- W2059643240 cites W2141236401 @default.
- W2059643240 cites W2157236463 @default.
- W2059643240 cites W2159127747 @default.
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- W2059643240 cites W2168186133 @default.
- W2059643240 cites W2331540308 @default.
- W2059643240 cites W91167684 @default.
- W2059643240 doi "https://doi.org/10.1016/j.ejmech.2009.11.035" @default.
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