Synthesis,antioxidative and antiviral activity of hydroxycinnamic acid amides of thiazole containing amino acid

The synthesis and the biological (antioxidant and antiviral) activities of novel hydroxycinnamic acid amides of a thiazole containing TFA.valine-4-carboxylic acid ethyl ester are reported. The amides have been synthesized from p-coumaric, ferulic and sinapic acids with the corresponding TFA.valine-thiazole-4-carboxylic acid ethyl ester using the coupling reagent N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4-(dimethylamino) pyridine (DMAP) as a catalyst. The antioxidant properties of the newly synthesized amides have been studied for then antioxidative activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH)* test. The newly synthesized compounds have been tested against the replication in vitro of influenza virus A (H3N2) and human herpes virus 1 and 2 (HSV-1 and HSV-2).     

Polyphenolic compounds in clove and pimento and their antioxidative activities

Two new polyphenolic glucosides, 6'-O-acetylisobiflorin (1) and (2S)-3-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol 1-O-(6'-O-galloyl)-β-D-glucoside (2), were respectively isolated from the flower buds of Syzygium aromaticum and berries of Pimenta dioica. Each structure was elucidated on the basis of spectral analyses (NMR, MS and [α](D)) and chemical conversion. A total of twenty-seven known compounds from the plants were also characterized. The antioxidative activity of their extracts and the twenty-nine isolates including gallo- and ellagitannins was estimated by oxygen radical absorbance capacity (ORAC) assay, and eugenol (3), which was the most abundant ingredient in each plant extract, showed the most potent antioxidative activity [ORAC value of 39,270 μmol TE (trolox equivalent)/g].     

灰树花多糖的提取及抗氧化活性

采用单因素和正交试验法对热水浸提、超声波辅助和微波辅助提取灰树花多糖的工艺进行研究,分别获得了3种方法的最佳条件,并发现微波辅助法最佳,其最优条件为:微波功率800 W、微波时间3 min,浸提2h,多糖得率为13.05％,比热水浸提法提高了51.22％.利用提取的灰树花多糖进行抗氧化性研究,发现灰树花多糖对O2-·和·OH都具有一定的清除作用,且多糖浓度与其对O2-·的清除作用存在量效关系,但不如·OH明显.     

Purification and properties of hydroxycinnamoyl CoA quinate hydroxycinnamoyl transferase from potatoes

A rapid method for the purification of hydroxycinnamoyl CoA quinate hydroxycinnamoyl transferase (CQT) from potato tubers which had been stored at low temperatures is described. The method involves affinity chromatography on Blue Sepharose with biospecific desorption of CQT with its substrate, CoA. Elution of the Blue Sepharose column with a gradient of CoA leads to the resolution of CQT, a protein with MW of ca 41500, into 3 peaks of activity; the largest peak elutes first. This fraction is purified × 1440 and gives a single band of protein after PAGE which suggests a high degree of purity. The properties of the 3 fractions of CQT, with respect to substrates and to a number of inhibitors, are described. The first and last eluting CQT fractions are specific for quinate and show no activity towards shikimate. The second peak, however, shows a small activity towards shikimate but this is thought to be due to an underlying peak of a shikimate specific enzyme. The major peak of CQT activity found in potatoes stored at 0° is absent from those stored at 10° throughout the period after harvest.     

Phenolic amides from the leaves of Nicotiana tabacum and their anti-tobacco mosaic virus activities

Three new phenolic amides, tabamides A–C (1–3), together with three known phenolic amides (4–6), were isolated from the leaves of Nicotiana tabacum. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D NMR techniques. Compounds 1–6 were also tested for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that compound 1 exhibited high anti-TMV activity with inhibition rate of 38.6%, which is higher than that of positive control (ningnanmycin). The other compounds also showed potential anti-TMV activity with inhibition rates in the range of 15.3–26.5%, respectively.     

低温弱光对黄瓜幼苗生长及抗氧化酶活性的影响

以设施栽培黄瓜为材料。研究了常温弱光和低温弱光胁迫期间以及随后的恢复过程中植株生长和抗氧化酶的变化．结果表明,常温弱光和低温弱光胁迫分别导致黄瓜植株生长减缓和停滞。根系活力下降．低温弱光处理过程中。SOD和GPOD活性上升,并以7℃处理尤为明显。但在恢复过程中这些酶的活性均恢复至对照水平．常温弱光对SOD活性影响不大,但在恢复过程中SOD活性则上升到一个比对照更高的水平,GPOD活性在弱光处理5d后迅速上升,恢复期间呈下降趋势．此外,常温弱光和低温弱光胁迫均造成MDA累积。     

Photosynthesis and antioxidative enzyme activities in five Indian mangroves with respect to their adaptability

Five typical mangroves were taken (Bruguiera gymnorrhiza, Excoecaria agallocha, Heritiera fomes, Phoenix paludosa and Xylocarpus granatum) both from Sundarbans (in situ) and grown in a mesophytic environment (ex situ, in the Institute’s premises) for 12–15 years. A comparative account of PAR utilization for maximum photosynthesis, stomatal conductance and production of two antioxidant enzymes (peroxidase and Superoxide dismutase) were done between the in situ and ex situ habitats. The present work revealed that the average net photosynthesis was slightly higher in mangroves from non-saline habitats than that of the native ones. At the same time, stomatal conductances were remarkably reduced under salinity-stressed habitats when compared with those of the mesophytic counterparts, by 25–52%. Salinity imposed increase of antioxidant enzymes was observed. Both the investigated antioxidant enzymes showed considerable increase in saline-grown individuals and proved their efficient scavenging ability to evolve reactive oxygen species (ROS), but these increases were relatively lower in Heritiera and Xylocarpus even though the net photosynthesis was higher. This might be related to their lower adaptability under increased salinity stress than those of the other three species investigated.     

DNA-binding and antiviral activities of bis-netropsins

The DNA-binding and antiviral activitus of bis-netropsins in which two monomers are attached covalently via three glycin residue were studied. These compounds have the same C-end groups but contain clusters with different numbers of lysine residues at the N-end of the molecule. In the homologous series of these compounds, bis-neropsins containing 15 and 31 branched lysine residues at the N-end of the molecule appear to be the most effective inhibitors of reproduction of the simplex herpes virus of type I in the Vero cell culture, including the virus versions resistant to aciclovir, ganciclovir, and other medicinal preparations. It was shown that the cytotoxicity of all the compounds studied is much lower than that of netropsin. The antiviral activity of the compounds correlates with their ability to selectively interact with the expanded clusters of the AT-pairs of DNA bases in the form of a monomer or a dimer, stabilized by interaction between the C-end halves of two bis-netropsin molecules bound at the neighboring overlapping binding sites on the DNA. The possible sites of their binding are the expanded clusters of AT-pairs at the origin of replication of OriS and OriL of the herpes virus.     

Synthesis of cinnamoyl and hydroxycinnamoyl amino acid conjugates and evaluation of their antioxidant activity.

Fifteen amides of cinnamic, ferulic and sinapic acids with natural and unnatural C-protected amino acids have been synthesized. The amides (E)-N-(feruloyl)-L-tyrosine methyl ester (10), (E)-N-(feruloyl)-L-phenylalanine t-butyl ester (11), (E)-N-(sinapoyl)-L-tyrosine methyl ester (13) and (E)-N-(sinapoyl)-L-phenylalanine t-butyl ester (15) with a free carboxyl group of amino acids have been found in nature. The rest of the compounds are unknown. The hydroxycinnamoyl amino acid conjugates have been studied for their antioxidant activity (AOA) in bulk phase lipid autoxidation. The highest AOA has been found for the compounds 11 and 15, which contain the same phenylalanine moiety.     

Synergistic antioxidative activities of hydroxycinnamoyl‐peptides

Antioxidants have become an important subject of study as an active ingredient for cosmetics and preservatives for food. We synthesized antioxidative peptide conjugates of hydroxycinnamic acids (HCAs) such as ferulic acid (FA), caffeic acid (CA), and sinapic acid (SA) by SPPS method. We measured their potential antioxidant properties by 2,2‐diphenyl‐1‐picrylhydrazyl radical (DPPH) scavenging test and lipid autoxidation inhibition test. When the antioxidative peptides, such as glutathione analogue (GS(Bzl)H) and carnosine (CAR), were conjugated to HCAs, their antioxidative activities were enhanced significantly. CA‐peptides exhibited the highest free radical scavenging activity by the DPPH test, and showed good antioxidative activity in the lipid autoxidation test. FA‐ and SA‐peptides showed excellent antioxidative activity in the lipid autoxidation test. Furthermore, we demonstrated a synergistic antioxidative activity of HCA‐peptide conjugates by comparing their antioxidative activity with that of a simple mixture of HCAs and the antioxidant peptides. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

Ansamycin derivatives from the marine-derived Streptomyces sp. SCSGAA 0027 and their cytotoxic and antiviral activities

Fourteen ansamycin derivatives including seven new herbimycins G–L (1–6) and divergolide O (7), and seven known analogues were isolated from a culture broth of the marine-derived Streptomyces sp. SCSGAA 0027. Their complete structures were determined by detailed analysis of spectroscopic data and quantum chemical calculations. Compounds 1–5 and 7 featured an additional eight-membered O-heterocycle that has rarely been reported for ansamycins, and the Z,Z- and E,E-configurations for Δ²,Δ⁴ were reported for the first time in geldanamycin analogues. Compound 1 exhibited weak inhibition activity towards Hsp90α with an IC₅₀ value of 96 µM, 2–5 showed mild cytotoxicity against four human cancer cell lines with IC₅₀ values ranging from 13 μM to 86 μM, and 7 had moderate anti-HSV-1 activity with an IC₅₀ value of 19 µM and very weak cytotoxicity towards Vero cell. The possible biosynthetic pathways for 1–5 were proposed. And their structure-bioactivity relationship was also discussed.     

Synthesis and antiviral activity of amides and conjugates of betulonic acid with amino acids

Betulonic acid amides with aliphatic and heterocyclic amines and with L-amino acids were synthesized by the acid chloride method. Betulonic acid amide and L-methionine derivatives of betulonic acid and its 3-oxime effectively inhibit the influenza A virus. Betulonic acid octadecylamide is active against the herpes simplex type 1 virus. The conjugate of betulonic acid 3-oxime with L-methionine is also active toward HIV-1. The tested compounds mainly show no activity toward the ECHO6 virus, which is devoid of a coat. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.     

Synthesis and antiviral activities of novel gossypol derivatives

In this study, a series of novel gossypol derivatives were synthesized and screened in vitro for their anti-HIV-1 and anti-H(5)N(1) activities, respectively. Replacing the aldehyde groups of gossypol with some amino acids not only reduced the cytotoxicity but also enhanced the activities against HIV-1 and H(5)N(1). Compounds 13-17 showed more potent activities against HIV-1 and H(5)N(1) than the other gossypol derivatives. Meanwhile, these compounds also exhibited more potent activities against H(5)N(1) than 1-adamantylamine. The absence of the COONa group in gossypol derivatives resulted in a loss of anti-HIV-1 activity, suggesting that this group might play an important role in mediating the antiviral activity. Time-of-addition assays indicated that compounds 13-17 had the similar mechanism of anti-HIV-1 action with T20. Molecular modeling analysis demonstrated that compounds 13-17 could fit inside the gp41 hydrophobic pocket through hydrogen bonding network, hydrophobic contacts and strong electrostatic interactions.     

Mitochondrial respiratory and antioxidative enzyme activities in turkey meat

Meat quality and (anti)oxidative metabolism of m. pectoralis superficialis (MPS), m. gastrocnemius (MG) and m. iliotibilialis lateralis (MIL) from turkey toms were analysed. After slaughter, pH of MPS and MG decreased and electrical conductivity of the MPS increased. The MG had generally higher pH values. The meat lightness (L) and redness (a) increased in MG and MPS after slaughter. The MPS always had higher L and lower a values. Mitochondrial respiratory activities (MRA) were higher in the MIL than the MPS. The activities of superoxide dismutase (SOD) and glutathione peroxidase, analysed in the MPS, increased and the glutathione reductase activity decreased after slaughter. Meat samples with lower pH24 h p.m. had higher drip loss and L values. The MRA were tendentially lower and the SOD activities higher in these samples. These results indicate a relation between the meat quality, the antioxidative metabolism and mitochondrial respiration.     

Assessment of UVB-photoprotective and antioxidative activities of carrageenan in keratinocytes

Ultraviolet B (UVB) (290–320 nm) is the foremost cause of photoaging, sunburn, wrinkles and skin cancer. Photoprotection against harmful UVB radiation is essential through various means including the use of skincare products. The seaweed polysaccharide carrageenan is widely used as an excipient in cosmetics and skincare products. However, its effects on normal skin keratinocytes or potential use as a photoprotective agent have yet to be established. The primary aim of this study was to assess the cytotoxic, photoprotective and antioxdative effects of carrageenan in UVB-induced immortalised normal human keratinocytes (HaCaT cells). Results showed that the percentage of cell viability decreased linearly with increasing UVB doses from 10, 50, 100, 222 to 1,000 mJ cm^?2. Four isomers of carrageenan, namely iota 2 [ι (??)], iota 5 [ι (V)], lambda (λ) and kappa (κ) carrageenan were used in this study. Vitamin E was used as a positive control. In terms of cytotoxicity, the CD₅₀ of kappa carrageenan was ~200 μg mL^?1 while for the other isomers, the values ranged from 122 to 162 μg mL^?1. Carrageenan showed significant protection against detrimental effects of UVB-induced cell killing and reactive oxygen species (ROS) release based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 2′,7′-dichlorfluorescein-diacetate (DCFH-DA) assays, respectively. Carrageenan was also able to quench 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. The ability to protect against UVB suggests that carrageenan has potential application as a photoprotective agent in addition to just being used as an excipient.     

Synthesis of dioxane-based antiviral agents and evaluation of their biological activities as inhibitors of Sindbis virus replication

The crystal structure of the Sindbis virus capsid protein contains one or two solvent-derived dioxane molecules in the hydrophobic binding pocket. A bis-dioxane antiviral agent was designed by linking the two dioxane molecules with a three-carbon chain having R,R connecting stereochemistry, and a stereospecific synthesis was performed. This resulted in an effective antiviral agent that inhibited Sindbis virus replication with an EC(50) of 14 microM. The synthesis proceeded through an intermediate (R)-2-hydroxymethyl-[1,4]dioxane, which unexpectedly proved to be a more effecting antiviral agent than the target compound, as evidenced by its EC(50) of 3.4 microM as an inhibitor of Sindbis virus replication. Both compounds were not cytotoxic in uninfected BHK cells at concentrations of 1mM.     

A comparative study of antioxidative activities of cell-wall polysaccharides

Oxidative burst in plants is elicited by biotic and abiotic stressors. Analogously to some monosaccharides which act as intracellular antioxidants, cell-wall polysaccharides may be in charge of buffering free-radical production in the extracellular compartment under pronounced prooxidative settings. Although a wide range of plant polysaccharides have been examined for their antioxidative properties, this usually has not been done in a coherent and comparative manner and against biologically relevant reactive species. Here we show that different cell-wall polysaccharides, cellulose, pectin, d-galacto-d-mannan, arabinogalactan, and xylan, exhibit distinctive antioxidative activities against the hydroxyl radical (OH)-generating Fenton reaction and superoxide. We found, using an EPR spin-trapping method, that the main carriers of ‘anti-Fenton’ activity in the plant cell wall are pectin and xylan. They most likely act by binding metal ions in such a manner to allow the Fenton reaction, after which they scavenge OH. Such a mode of action is preferred by cells resulting in a safe degradation of H₂O₂. On the other hand, the polysaccharides examined showed similar superoxide scavenging capacities. We propose that plants may employ different antioxidative characteristics of polysaccharides to regulate their redox status by modifying the composition of the cell wall.     

Lichen secondary metabolites from the cultured lichen mycobionts of Teloschistes chrysophthalmus and Ramalina celastri and their antiviral activities

Lichens and spore-derived cultured mycobionts of Teloschistes chrysophthalmus and Ramalina celastri were studied chemically, and results indicated that they produced, respectively, parietin and usnic acid as major secondary metabolites, which were purified and identified. Identification of the compounds was performed by high performance liquid chromatography and structural elucidation by nuclear magnetic resonance (1H) and electron impact mass spectrometry. Usnic acid exhibited antiviral activity whereas parietin had a virucidal effect against the arenaviruses Junin and Tacaribe.