113482-94-3Relevant articles and documents
Antioxidative activity of tetrahydrocurcuminoids.
Osawa,Sugiyama,Inayoshi,Kawakishi
, p. 1609 - 1612 (1995)
In order to develop a new type of antioxidative compound which has both the phenolic and beta-diketone moiety in the same molecule, we converted three known curcuminoids, curcumin (diferuloylmethane, U1), (4-hydroxy-3-methoxycinnamoyl)methane (U2), and bis-(4-hydroxycinnamoyl)methane (U3), which are the natural antioxidants of Curcuma longa L. (tumeric), to tetrahydrocurcuminoids (THU1, THU2, and THU3, respectively) by hydrogenation, and evaluated their antioxidative activity by using linoleic acid as the substrate in an ethanol/water system. Further, we used the rabbit erythrocyte membrane ghost and rat liver microsome as in vitro systems and determined the antioxidative activity of these curcuminoids. When we evaluated their antioxidative activity by these assays, it was found that THU1 had the strongest antioxidative activity among all curcuminoids in each assay system. THU1 has been reported to be one of the main metabolites of U1 in vivo [Holder et al., Xenobiotica, 8, 761-768 (1978)]. These results suggest that THU1 must play an important role in the antioxidative mechanism of U1 in vivo by converting U1 into THU1.
Identification of a new curcumin synthase from ginger and construction of a curcuminoid-producing unnatural fusion protein diketide-CoA synthase::curcumin synthase
Zhang, Le,Gao, Bowen,Wang, Xiaohui,Zhang, Zhongxiu,Liu, Xiao,Wang, Juan,Mo, Ting,Liu, Yuyu,Shi, Shepo,Tu, Pengfei
, p. 12519 - 12524 (2016/02/12)
The biosynthesis and metabolic engineering of curcuminoids received considerable attention for their important pharmaceutical properties. In the present study, a new curcumin synthase (ZoCURS) was identified from ginger (Zingiber officinale). Notably, ZoCURS efficiently accepts 3-(4-hydroxyphenyl)propionyl-CoA to produce tetrahydrobisdemethoxycurcumin, which would be meaningful to further understand the biosynthesis of curcuminoids in ginger. In addition, a curcuminoid-producing unnatural fusion protein diketide-CoA synthase::curcumin synthase (DCS::CURS) was constructed. Comparing to ZoCURS, DCS::CURS indicated similar substrate specificities and catalytic potentials to catalyze the formation of various curcuminoids, however, the yield of curcuminoids produced by DCS::CURS was obviously increased, which would be useful for metabolic engineering of pharmaceutically important curcuminoid analogs, particularly including asymmetric dihydrocurcuminoids such as 3-(4-hydroxyphenyl)propionyl-feruloylmethane, 3-(4-hydroxyphenyl)propionyl-p-coumaroylmethane, and 3-(4-hydroxyphenyl)propionyl-cinnamoylmethane.
Curcuminoid analogs with potent activity against Trypanosoma and Leishmania species
Changtam, Chatchawan,de Koning, Harry P.,Ibrahim, Hasan,Sajid, M. Sohail,Gould, Matthew K.,Suksamrarn, Apichart
experimental part, p. 941 - 956 (2010/04/24)
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.
