Cancer preventive mechanisms of the green tea polyphenol (-)-epigallocatechin-3-gallate

Accumulating evidence indicates that consumption of tea, especially green tea, is good for preventing cancer. To elucidate the cancer preventive mechanisms of green tea, much effort has been devoted to investigating the anticancer effects of (-)-epigallocatechin-3-gallate (EGCG), the major component of green tea. It has been revealed that EGCG restrained carcinogenesis in a variety of tissues through inhibition of mitogen-activated protein kinases (MAPK), growth factor-related cell signaling, activation of activator protein 1 (AP-1) and nuclear factor-B (NF-kappaB), topoisomerase I, matrix metalloproteinases and other potential targets. Therefore, EGCG is a multipotent anticancer agent, which not only provides solid evidence to support the anticancer potential of green tea, but also offers new clues for discovering multiple-targeted anticancer drugs.     

(-)-Epicatechin-3-gallate, a green tea polyphenol is a potent agent against UVB-induced damage in HaCaT keratinocytes

(-)-Epicatechin-3-gallate (ECG) is a polyphenolic compound similar to (-)-epigallocatechin-3-gallate (EGCG) which is abundant in green tea. Numerous workers have proposed that EGCG protects epidermal cells against UVB-induced damage. However, little has been known about whether ECG protects keratinocytes against UVB-induced damage. We decided to investigate the protective effects and underlying mechanisms of ECG on UVB-induced damage. Cell viability was determined by the MTT assay. Activation of ERK1/2, p38 and JNK was analyzed by Western blotting. Intracellular H2O2 production and DNA content was analyzed by flow cytometry. Lipid peroxidation was assayed by colorimetry. In our study, we found that ECG dose-dependently attenuated UVB-induced keratinocyte death. Moreover, ECG markedly inhibited UVB-induced cell membrane lipid peroxidation and H2O2 generation in keratinocytes, suggesting that ECG can act as a free radical scavenger when keratinocytes were photodamaged. In parallel, H2O2-induced the activation of ERK1/2, p38 and JNK in keratinocytes could be inhibited by ECG. UVB-induced pre-G1 arrest leading to apoptotic changes of keratinocytes were blocked by ECG. Taken together, we provide here evidence that ECG protects keratinocytes from UVB-induced photodamage and H2O2-induced oxidative stress, possibly through inhibition of the activation of ERK1/2, p38 and JNK and/or scavenging of free radicals.     

Enantioselective synthesis of epigallocatechin-3-gallate (EGCG), the active polyphenol component from green tea

[reaction: see text]. Enantioselective synthesis of epigallocatechin-3-gallate (EGCG, 3b), the active polyphenol component from green tea, has been achieved by using a stereospecific cyclization of the Sharpless asymmetric dihydroxylation product 7c as the key step.     

Nanochemoprevention by encapsulation of (-)-epigallocatechin-3-gallate with bioactive peptides/chitosan nanoparticles for enhancement of its bioavailability

Nanochemoprevention by oral consumption was developed by the encapsulation of (-)-epigallocatechin-3-gallate (EGCG) with nanoparticles that were electrostatically assembled from bioactive caseinophosphopeptides and chitosan, which was highly biocompatible and able to enhance the bioavailability of EGCG.     

Structural identification of novel glucoside and glucuronide metabolites of (-)-epigallocatechin-3-gallate in mouse urine using liquid chromatography/electrospray ionization tandem mass spectrometry

(-)-Epigallocatechin-3-gallate (EGCG), the most abundant and most biologically active polyphenolic compound in tea, has been proposed to have many health beneficial effects. The metabolic fate of EGCG, however, is not well understood. In the present study, we identified a novel EGCG metabolite, 7-O-beta-D-glucopyranosyl-EGCG-4'-O-beta-D-glucupyranoside, in a mouse urine sample using liquid chromatography/electrospray ionization tandem mass spectrometry. The structure of this metabolite was confirmed by analyzing the MSn (n = 1-4) spectra as well as comparing the MS/MS spectra of its product ions with those from EGCG and EGCG-4'-O-beta-D-glucupyranoside standards. To our knowledge, this is the first report of the identification of a glucoside metabolite of EGCG in mammals. Our results indicate that glucosidation represents a novel pathway in the metabolism of EGCG in mice.     

Synthesis of phosphates and phosphates-acetates hybrids of green tea polyphenol (−)-epigallocatechine-3-gallate (EGCG) and its G ring deoxy analogs as potential anticancer prodrugs

A series of phosphate or phosphate-acetate hybrid modified EGCG or EGCG G ring deoxy analogs were synthesized by a convenient semi-synthesis strategy from the abundant natural compound EGCG.     

Synthesis of a 3,4,5-trimethoxybenzoyl ester analogue of epigallocatechin-3-gallate (EGCG): a potential route to the natural product green tea catechin, EGCG

The synthesis of a trimethoxybenzoyl ester (D-ring) analogue of epigallocatechin-3-gallate (EGCG) is described. The versatile synthesis route can be used to synthesize A, B, and D ring analogues of EGCG and involves a key cyclization of the chalcone to the 3-flavene. This synthesis provides a possible route to the polyphenolic green tea natural product EGCG.     

Determination of total antioxidant capacity in green tea by near-infrared spectroscopy and multivariate calibration

A principal component regression (PCR) model is built for prediction of total antioxidant capacity in green tea using near-infrared (NIR) spectroscopy. The modelling procedures are systematically studied with the focus on outlier detection. Different outlier detection methods are used and compared. The root mean square error of prediction (RMSEP) of the final model is comparable to the precision of the reference method.     

Colloidal complexes from associated water soluble cellulose derivative (methylcellulose) and green tea polyphenol (Epigallocatechin gallate)

The present work deals with the preparation and characterisation of colloidal complexes from association of water soluble cellulose derivative (methylcellulose) and green tea polyphenol-EGCG (Epigallocatechin gallate). Colloidal complexes with well defined size range of 95-300 nm (polydispersity index<0.15) and a negative surface potential (-25 to -45 mV) were obtained by mixing solutions of methylcellulose and EGCG under vigorous stirring. The binding stoichiometry of 21 molecules of EGCG per one molecule of polymer was obtained from isothermal titration calorimetry. The free energy of binding (-31 kJ mol(-1)) is dominated by the binding enthalpy suggesting that the non-covalent complex is preferentially formed due to the hydrogen bonding. Transmission electron microscopy revealed almost spherical particle morphology of the formed colloidal complexes. Further, sustained release of EGCG from the complex in simulated in vitro media was observed which resulted in protecting the antioxidant property of EGCG in alkaline pH.     

Evaluation of antioxidant and anti-inflammatory activity of green coffee beans methanolic extract in rat skin

Abstract

Since a long time caffeine has been used in pharmaceutical and cosmetic preparations due to its favorable effects on the skin. The aim of this study was to evaluate the topical anti-inflammatory activity (carrageenan-induced paw oedema) of an ointment prepared using a methanolic extract from green beans of C. robusta via histology. Results showed that the treatment with the ointment reduced the paw oedema within 3 and 5?h post-carrageenan administration. The immunohistochemical evaluations of αSMA, Langerin and S100 gave further support to the morphological analysis. Finally, the methanolic extract from green beans of C. robusta proved to possess elevated free radical scavenger capability by DPPH assay, which may contribute to the observed anti-inflammatory activity.     

Synthesis,antioxidant, and antimicrobial activity of 3-(1H-indole-3-carbonyl)-2H-chromen-2-ones

A simple and convenient method for the one-pot synthesis of 3-(1H-indole-3-carbonyl)-2H-chromen-2-one derivatives from the reaction of 3-cyanoacetyl indole and salicylaldehyde in the presence of Na₂CO₃ in water: methanol (1:1) is described. Wider substrate scope, high yields, operational simplicity, and simple purification process make the protocol highly applicable in the synthesis of 3-(1H-indole-3-carbonyl)-2H-chromen-2-ones. For the first time, in vitro antioxidant and antimicrobial activity was studied. Compounds 5e , 7a , and 7b exhibits good radical scavenging ability against DPPH free radical. Compounds 7b , 5f , and 5g possess lower EC₅₀ values than the Standards AA and BHA and thus proving their high reducing power. Compounds 5d and 5f show good antibacterial activity against gram-positive bacteria (MRSA) while compounds 5c , 7a , and 7b exhibits good antibacterial activity against Bacillus sp. Compounds 5b and 5e show good antibacterial activity against gram negative bacterial strains (Escherichia coli, Klebsiella pneumoniae) and compounds 5g and 5h exhibits good antifungal activity against Candida albicans.     

Pyridine and pyrimidine ring syntheses from 4-(4-morpholino)-3-pentenone and from ethyl 3-(4-morpholino)-2-butenoate

3-Substituted 2(1H)-pyridones are produced from reaction of 4-(4-morpholino)-3-pentenone 1 with each of the following carbon acids: cyanoacetamide, malononitrile, cyanothioacetamide, acetylacetamide, benzoyl-acetonitrile. Reaction of ethyl 3-(4-morpholino)-2-butenoate 2 with cyanoacetamide gives the corresponding hydroxypyridone. Pyrimidines are formed by reaction of 1 and of 2 with benzamidine and with S-benzylthio-urea; in the last case, the eliminated morpholine displaces the benzylthio group to give the final product.     

A novel urocanic acid derivative from skin tissue extracts; (E)-3-[1-(1,1-dimethyl-3-oxobutyl)imidazol-4-yl]propenoic acid

A novel derivative of urocanic acid ( 1 ) had been isolated from acetone extracts of rabbit skin tissue. It proved to be (E)-3-[1-(1,1-dimethyl-3-oxobutyl)imidazol-4-yl]propenoic acid ( 3c ), potentially a much better ultraviolet screening agent than urocanic acid. Sterical effect of dimethyl groups in the side chain adjacent to the imidazole ring of 3c on its solubility is also discussed.     

Preparation,molecular structures,and characteristic properties of (E)-1-(2-furyl)- and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylenes and (E)-1-(3-furyl)- and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylenes

Wittig reactions of 2-furaldehyde (20) [and thiophene-2-carbaldehyde (21)] with (3-guaiazulenylmethyl)triphenylphosphonium bromide (19) in ethanol containing NaOEt at 25 °C for 24 h under argon give (E)-1-(2-furyl)-2-(3-guaiazulenyl)ethylene (22E) and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylene (23E) in 53 and 36% yields. Similarly, Wittig reactions of 3-furaldehyde (29) [and thiophene-3-carbaldehyde (30)] with 19 under the same reaction conditions as for 20 and 21 afford (E)-1-(3-furyl)-2-(3-guaiazulenyl)ethylene (31E) and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylene (32E) in 32 and 46% yields. Molecular structures and characteristic properties as well as preparation of the title E (i.e., one of the geometrical isomers) forms, with a view to comparative study, are reported. Moreover, reactions of those conjugated π-electron systems with TCNE (=tetracyanoethylene) in benzene [and in DMF (=N,N-dimethylformamide)] at 25 °C for 24 h under argon yield unique products, possessing interesting molecular structures, respectively, whose characteristic properties and crystal structures are documented, also.     

UVB-induced conversion of 7-dehydrocholesterol to 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in the human keratinocyte line HaCaT

We have previously shown that keratinocytes in vitro can convert biologically inactive vitamin D3 to the hormone calcitriol. The present study was initiated to test whether ultraviolet B (UVB)-induced photolysis of provitamin D3 (7-dehydrocholesterol, [7-DHC]) which results in the formation of vitamin D3 also leads to the generation of calcitriol in keratinocytes. Submerged monolayers of HaCaT keratinocytes were preincubated with 7-DHC (25 microM) at 37 degrees C and irradiated with monochromatic UVB at different wavelengths (effective UV-doses: 7.5-60 mJ/cm2), or a narrow-band fluorescent lamp Philips TL-01 (UVB-doses: 125-1500 mJ/cm2). Irradiation with both sources of UVB resulted in the generation of different amounts of previtamin D3 in our in vitro model followed by time-dependent isomerization to vitamin D3 and consecutive formation of calcitriol in the picomolar range. Unirradiated cultures or cultures exposed to wavelengths > 315 nm generated no or only trace amounts of calcitriol. The conversion of vitamin D3 generated after UVB irradiation to calcitriol is inhibited by ketoconazole indicating the involvement of P450 mixed function oxidases in this chemical reaction. The generation of calcitriol was wavelength- and UVB dose dependent and reached approximately 18-fold higher levels after irradiation at 297 nm than at 310 nm (effective UVB dose: 30 mJ/cm2). Hence, keratinocytes may be a potential source of biologically active calcitriol within epidermis, when irradiated with therapeutical doses of UVB.     

Secondary Acetylenic Alcohols and Peroxides Derived from (Z)-3-chloro-3-(2-naphthyl)-2-propenal

Secondary acetylenic alcohols were obtained by reactions of 1-hexynyl-, 2-phenylethynyl, and tert-alkylperoxyalkynyllithiums with (Z)-3-chloro-3-(2-naphthyl)-2-propenal. Thermal stability of the peroxides synthesized was assessed by thermal analysis.     

3-(1′-hydroxyethyl)-2-azetidinones from 3-hydroxybutyrates and n-arylaldimines

Dianion imine addition, cyclisation reaction between ethyl-3-hydroxybutyrate and aldimines generates β-lactams with the hydroxyethyl sidechain of thienamycin and related β-lactam antibiotics in place. The effects of the N-arylaldimine and the reaction conditions on the stereochemistry of the resulting products are examined.     

Dietary burden of phenolics per serving of "Mountain tea" (Sideritis) from Macedonia and correlation to antioxidant activity

This work was afforded from 2 points of view, phytochemical evaluation and relation to antioxidant activity and dietary burden of phenolics of a cup of "Mountain tea", a drink obtained by domestic infusion of Sideritis. Phytochemically, two extraction protocols using water and methanol as solvent were used for comparison. Methanol and boiling water extracts (by domestic infusion procedure) showed that extracts were rich in bound forms of phenolics such as hydroxycinnamic acids, phenylethanoid glycosides and flavonoid glycosides. The total phenolic content for Sideritis species ranged around 190 mg per serving (2 g infusion bag) for methanol extracts and around 72 mg per serving in water extracts. Among the two different Macedonian Sideritis species, Sideritis raeseri (wild growing) showed the highest phenolics content in both extracts (212 mg and 89 mg per serving, respectively). Concerning the phenolic content in the different aerial parts, leaf was the richest plant organ in phenolics followed by flower and stem with the lowest amount. The methanol extract from Sideritis raeseri (wild growing) showed the highest antioxidant capacity as shown by DPPH, ABTS and FRAP assays. The antioxidant capacity was linearly correlated with phenolic content. Nutritionally, the dietary burden of phenolics of a "Mountain tea" bag for domestic infusion (serving size) was established at 89 mg for an homogeneous and equal distribution of the different aerial parts (leaf, flower and stem). However, and according to our results a rate of 60% leaf and 40% flower would increase the content of bioavailable phenolics and also the total phenolics content of a serving bag of "Mountain tea".     

Novel (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles from (E)- and (Z)-3-styrylchromones: the unexpected case of (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles

An efficient synthetic method for the preparation of (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles has been developed. The reaction of (E)- and (Z)-3-styrylchromones with hydrazine hydrate afforded the corresponding (E)- and (Z)-4-styrylpyrazoles, respectively, saved 4′-nitro-derivatives where both (E)- and (Z)-4′-nitro-3-styrylchromones afforded (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles. The reaction mechanism for these transformations was discussed and the stereochemistry of all products was assigned by NMR experiments.     

Synthesis of 3-Aroyl-2-(polyfluoroalkyl)quinoxalines and 3-Aroyl-2-(polyfluoroalkyl)benzo[g]quinoxalines from Lithium 3-(Fluoroalkyl)-1,3-diketonates

Russian Journal of Organic Chemistry - A one-pot procedure has been developed for the synthesis of 3-aroyl-2-(polyfluoroalkyl)quinoxalines and 3-aroyl-2-(polyfluoroalkyl)benzo[g]quinoxalines by...