93559-28-5

Upstream product

• 98885-93-9 curcumin 
• 93559-23-0 4-(2-{2-[4-(4-Benzyloxy-3-methoxy-phenyl)-2-hydroxy-butyl]-[1,3]dioxolan-2-yl}-ethyl)-2-methoxy-phenol 
• 36062-04-1 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione 
• 147556-16-9 curcumin 
• 1360109-97-2 (S)-1-((S)-4-benzyl-2-thioxothiazolidin-3-yl)-5-(4-(benzyloxy)-3-methoxyphenyl)-3-hydroxypentan-1-one 
• 1360109-98-3 (S)-1-((S)-4-benzyl-2-thioxothiazolidin-3-yl)-5-(4-(benzyloxy)-3-methoxyphenyl)-3-(methoxymethoxy)pentan-1-one 
• 1360110-00-4 (S)-5-(4-(benzyloxy)-3-methoxyphenyl)-3-(methoxymethoxy)pentanal 
• 1360110-02-6 (S)-1,7-bis(4-(benzyloxy)-3-methoxyphenyl)-5-(methoxymethoxy)hept-1-yn-3-one 
• 2426-87-1 3-methoxy-4-(phenylmethoxy)benzaldehyde 
• 57371-44-5 3-<4-(benzyloxy)-3-methoxyphenyl>propan-1-ol 
• 38157-08-3 (E)-3-(4-benzyloxy-3-methoxyphenyl)acrylic acid ethyl ester 
• 458-37-7 curcumin 
• 144735-54-6 1-ethynyl-4-(benzyloxy)-3-methoxybenzene 
• 69172-20-9 3-(3-methoxy-4-benzyloxyphenyl)propionaldehyde 

Downstream Products

• 79067-88-2 1,7-bis-(4-hydroxy-3-methoxyphenyl)-4-hepten-3-one 
• 135308-89-3 Acetic acid 4-[(3S,5R)-3,5-diacetoxy-7-(4-acetoxy-3-methoxy-phenyl)-heptyl]-2-methoxy-phenyl ester 
• 153381-09-0 (3R,5S)-3,5-Dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane 
• 112494-41-4 (3S,5S)-3,5-Dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane 
• 41137-87-5 hirsutenone 
• 79067-88-2 (E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-hepten-3-one 

Relevant academic research and scientific papers

Pharmacognostic studies on ginger and related drugs - Part 1: Five sulfonated compounds from Zingiberis rhizome (Shokyo)

Five sulfonated compounds, namely 4-gingesulfonic acid and shogasulfonic acids A, B, C and D, were isolated together with seven known compounds including 6-gingesulfonic acid from Zingiberis rhizome (Japanese name: Shokyo) made out of ginger. Their struct

Hexahydrocurcumin ameliorates hypertensive and vascular remodeling in L-NAME-induced rats

Hexahydrocurcumin (HHC), a major metabolite of curcumin, possesses several biological activities such as antioxidant, anti-inflammation, and cardioprotective properties. This study aimed to investigate the effect of HHC on high blood pressure, vascular dy

Pharmacokinetics-driven evaluation of the antioxidant activity of curcuminoids and their major reduced metabolites—a medicinal chemistry approach

Curcuminoids are the main bioactive components of the well-known Asian spice and traditional medicine turmeric. Curcuminoids have poor chemical stability and bioavailability; in vivo they are rapidly metabolized to a set of bioreduced derivatives and/or glucuronide and sulfate conjugates. The reduced curcuminoid metabolites were also reported to exert various bioactivities in vitro and in vivo. In this work, we aimed to perform a comparative evaluation of curcuminoids and their hydrogenated metabolites from a medicinal chemistry point of view, by determining a set of key pharmacokinetic parameters and evaluating antioxidant potential in relation to such properties.Reduced metabolites were prepared from curcumin and demethoxycurcumin through continuous-flow hydrogenation. As selected pharmacokinetic parameters, kinetic solubility, chemical stability, metabolic stability in human liver microsomes, and parallel artificial membrane permeability assay (PAMPA)-based gastrointestinal and blood-brain barrier permeability were determined. Experimentally determined logP for hydrocurcumins in octanol-water and toluene-water systems provided valuable data on the tendency for intramolecular hydrogen bonding by these compounds. Drug likeness of the compounds were further evaluated by a in silico calculations. Antioxidant properties in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and oxygen radical absorbance capacity (ORAC) assays were comparatively evaluated through the determination of ligand lipophilic efficiency (LLE). Our results showed dramatically increased water solubility and chemical stability for the reduced metabolites as compared to their corresponding parent compound. Hexahydrocurcumin was found the best candidate for drug development based on a complex pharmacokinetical comparison and high LLE values for its antioxidant properties. Development of tetrahydrocurcumin and tetrahydro-demethoxycurcumin would be limited by their very poor metabolic stability, therefore such an effort would rely on formulations bypassing first-pass metabolism.

Use of curcumin derivative

The invention provides the use of a curcumin derivative. The use of the curcumin derivative shown in a formula I (please see the specification for the formula), or salts of the curcumin derivative inthe preparation of drugs of anti-inflammatory diseases and/or a COX inhibitor is particularly provided. The curcumin derivative has good COX inhibitory activity and anti-inflammatory activity and canbe used for preparing the COX inhibitor and anti-inflammatory drugs. Compound 6 and compound 7 have the best effects on COX-2 inhibitory activity and anti-inflammatory activity and can be used for preparing a COX-2 inhibitor and the anti-inflammatory drugs.

FOOD COMPOSITION FOR PREVENTING OBESITY, PHARMACEUTICAL COMPOSITION FOR TREATING OBESITY, AND ANIMAL MEDICINE FOR TREATING OBESITY, CONTAINING GINGERNONE A

Disclosed is a composition comprising gingerenone A as an active ingredient. The composition includes a food composition for preventing obesity, a pharmaceutical composition for treating obesity and a medicine for treating animal obesity. Since the composition includes gingerenone A, which inhibits expression of the important transcriptional factors C/EBPα and PPARγ, expressed upon adipocyte differentiation, as well as FAS protein expression, the composition has superior potential for obesity prevention or treatment.

Synthesis and evaluation of curcumin derivatives toward an inhibitor of beta-site amyloid precursor protein cleaving enzyme 1

To research a new non-peptidyl inhibitor of beta-site amyloid precursor protein cleaving enzyme 1, we focused on the curcumin framework, two phenolic groups combined with an sp2 carbon spacer for low-molecular and high lipophilicity. The structure-activity relationship study of curcumin derivatives is described. Our results indicate that phenolic hydroxy groups and an alkenyl spacer are important structural factors for the inhibition of beta-site amyloid precursor protein cleaving enzyme 1 and, furthermore, non-competitive inhibition of enzyme activity is anticipated from an inhibitory kinetics experiment and docking simulation.

Curcuminoid analogs inhibit nitric oxide production from LPS-activated microglial cells

The chemically modified analogs, the demethy-lated analogs 4-6, the tetrahydro analogs 7-9 and the hexahydro analogs 10-12, of curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) were evaluated for their inhibitory activity on lipopolysaccharide activated nitric oxide (NO) production in HAPI microglial cells. Di-O-demethylcurcumin (5) and O- demethyldemethoxycurcumin (6) are the two most potent compounds that inhibited NO production. The analogs 5 and 6 were twofold and almost twofold more active than the parent curcuminoids 1 and 2, respectively. Moreover, the mRNA expression level of inducible NO synthase was inhibited by these two compounds. The strong neuroprotective activity of analogs 5 and 6 provide potential alternative compounds to be developed as therapeutics for neurological disorders associated with activated microglia. The Japanese Society of Pharmacognosy and Springer 2011.

Synthesis of gingerol and diarylheptanoids

The synthesis of gingerol 1 and related compounds 2-5 along with diarylheptanoids 6-8 has been accomplished using a Keck allylation, Crimmins' aldol reaction, aldehyde coupling with acetylene, and chelation controlled reductions as the key reactions. The absolute configuration of these molecules was confirmed by preparing their acetonide derivatives and by comparison of the NMR data with natural compounds.

Autoxidative and cyclooxygenase-2 catalyzed transformation of the dietary chemopreventive agent curcumin

The efficacy of the diphenol curcumin as a cancer chemopreventive agent is limited by its chemical and metabolic instability. Non-enzymatic degradation has been described to yield vanillin, ferulic acid, and feruloylmethane through cleavage of the heptadienone chain connecting the phenolic rings. Here we provide evidence for an alternative mechanism, resulting in autoxidative cyclization of the heptadienone moiety as a major pathway of degradation. Autoxidative transformation of curcumin was pH-dependent with the highest rate at pH 8 (2.2 μM/min) and associated with stoichiometric uptake of O 2. Oxidation was also catalyzed by recombinant cyclooxygenase-2 (COX-2) (50 nM; 7.5 μM/min), and the rate was increased ≈10-fold by the addition of 300 μM H2O2. The COX-2 catalyzed transformation was inhibited by acetaminophen but not indomethacin, suggesting catalysis occurred by the peroxidase activity. We propose a mechanism of enzymatic or autoxidative hydrogen abstraction from a phenolic hydroxyl to give a quinone methide and a delocalized radical in the heptadienone chain that undergoes 5-exo cyclization and oxygenation. Hydration of the quinone methide (measured by the incorporation of O-18 from H218O) and rearrangement under loss of water gives the final dioxygenated bicyclopentadione product. When curcumin was added to RAW264.7 cells, the bicyclopentadione was increased 1.8-fold in cells activated by LPS; vanillin and other putative cleavage products were negligible. Oxidation to a reactive quinone methide is the mechanistic basis of many phenolic anti-cancer drugs. It is possible, therefore, that oxidative transformation of curcumin, a prominent but previously unrecognized reaction, contributes to its cancer chemopreventive activity.

Microbial transformation of curcumin by Rhizopus chinensis

Curcumin (1) is a potent antioxidant and antitumor natural product. In spite of its efficacy and safety, its clinical use is hindered mainly by poor water solubility and bioavailability. Structural modification to introduce hydrophilic functions is a promising approach to resolve this problem. In the present study we first found that curcumin could be efficiently converted into glucosides by filamentous fungi including Rhizopus chinensis IFFI 03043, Absidia coerulea AS 3.3389 and Cunninghamella elegans AS 3.1207. Curcumin 4′-O-β-d-glucoside (2), together with hexahydrocurcumin (3), was isolated from a preparative-scale biotransformation with R. chinensis IFFI 03043 and characterized fully by NMR and MS. A time-course study revealed that curcumin could be efficiently converted into curcumin 4′-O-β-d- glucoside within 8 h when administered at 0.05 mmol L-1 and the productivity was 57%. Additionally, the biotransformation products of curcumin by different fungal strains were analyzed by LC/MS. At least 15 metabolites were detected, and the predominant biotransformation reaction was glucosylation. This study provides a simple, efficient and less expensive approach for the preparation of curcumin glucosides. The introduction of the glucosyl function might be able to enhance the bioavailability of curcumin.