Structural modification of phenylpropanoid-derived compounds and the effects on their participation in redox processes

Oxidation and reduction processes are fundamental to many of the proposed mechanisms by which dietary phytochemicals are thought to exert protective effects against cardiovascular disease and some cancers. An understanding of the redox chemistry of these compounds is essential in assessing their potential to participate in these processes. Phenylpropanoid-derived compounds were selected and synthesised where required to represent many of the structural features found in this important group of compounds. Using electron paramagnetic resonance spectroscopy and computational chemistry a structure-redox activity relationship was obtained. Good correlation of computational and experimental results was observed for the mono-hydroxylated compounds. This demonstrated the value of computational chemistry in obtaining information about compounds, not readily available and the effect of electron delocalisation on parent radical stability. For compounds containing more than one hydroxyl, the relationship was found to be more complex. The importance of quinone formation in compounds containing more than one hydroxyl substituent was highlighted, as this was found to have a significant effect on stabilisation and therefore, their participation in redox processes.     

Quantification of Compositional Changes of Petroleum Hydrocarbons by GC/FID and GC/MS during a Long-Term Bioremediation Experiment

Samples from a long-term bioremediation experiment contaminated with two crude oils, Arabian Heavy and Gullfax, was used to analyze the compositional change of petroleum hydrocarbons. A time course of five different homologous series of petroleum hydrocarbons were analysed by GC/FID and GC/MS. The homologous series were n-alkanes, acyclic isoprenoids, alkylated naphthalenes, alkylated phenanthrenes, and alkylated dibenzothiophenes. Several biomarker compounds were monitored during the experiment to evaluate the possible use as conserved reference compounds for the quantification of other oil compounds, that is, nor-hopanes, hopanes, methyl-hopanes, steranes, mono- og triaromatic steranes. The 17α(H),21β(H)-hopane was found to be stable toward biodegradation and was used as reference compound. The internal standard quantification method was used to quantify changes of the homologous series of oil compounds, and a graphic presentation was used to compare the decrease of the individual compounds. This was found to be an easy way of comparing relative changes in oil. The disappearance of the compounds was extensive and in 6 to 7 months less than 6% remained. The decrease of the n-alkanes (>C15) and acyclic isoprenoids was almost uniform within each homologous series and thus independent of physical-chemical characteristics. Evaporation affected compounds with boiling points lower than n-C15. The alkylated aromatic and sulfur-aromatic compounds decreased according to the degree of alkylation and the decrease showed to be delayed by 10 to 20% by each additional alkyl group. The lack of isomeric-specific degradation of most of the aromatic and sulfur-aromatic compounds, until extensive decrease in concentration had occurred, suggests these compounds have to be dissolved, before any biodegradation occurs.     

Stimulating Effects of Organic Solvents on the Mutagenicities of Sugar-degradation Compounds

Most of the organic solvents tested were found to stimulate the mutagenicities of some mutagenic compounds. These stimulated compounds were restricted to the sugar-degradation products among various mutagenic compounds. From reduction of Nitro Blue tetrazolium (NBT), it can be said that all of the sugar-degradation compounds tested formed oxygen radicals in alkali conditions by autoxidation, and it was confirmed that the rates of the reducion of NBT by these compounds were greatly stimulated by various organic solvents. Further, the depolymerization of DNA by sugar-degradation compounds was found to stimulated by organic solvents. These results demonstrate that organic solvents enhance the oxygen radical formation of these sugar-degradation compounds, which leads to the stimulation of their mutagenicity.     

Diversity of phenolic compounds and plant traits in coexisting Patagonian desert shrub species of Argentina

Desert shrubs often accumulate different types of phenolic compounds but what determines the amount and diversity of these compounds is an issue scarcely explored. The aim of this study was to assess differences in the amount and diversity of phenolic compounds in leaves among coexisting shrub species differing in rooting depth and leaf turnover. We hypothesized that the diversity and amount of phenolic compounds in leaves of desert shrubs are related to access to soil water through rooting depth, and to leaf turnover. The study was carried out in the Patagonian Monte of Argentina. We collected green leaves of six species representing the dominant shrub morphotypes (tall evergreen, tall deciduous, and medium evergreen shrubs) and assessed lignin concentration and groups of soluble phenols obtained by sequential extraction with ethyl ether, ethyl acetate, and amyl alcohol. We also assessed nitrogen concentration in leaves and leaf mass per unit area (LMA) as traits related to leaf lifespan. The diversity of phenolic compounds was higher in green leaves of tall shrubs with deep rooting depth than in those of medium evergreen shrubs with shallow rooting depth. Diversity of phenolic compounds in green leaves was negatively related to lignin concentration. Evergreen shrubs had higher amount of phenolic compounds in green leaves than deciduous ones and the total amount of phenolic compounds in green leaves was positively related to LMA. We concluded that access to soil water sources and leaf turnover were related to the amount and diversity of phenolic compounds in green leaves of desert shrub species and these results are consistent with those predicted by the resource availability theory for plants from resource-rich and resource-poor habitats.     

Isolation, purification, and partial chemical characterization of chromium(III) fractions existing in brewer's yeast and Sabouraud's liquid medium.

An ethanol extract of brewer's yeast which had been cultivated in a medium containing trivalent 51Cr was analyzed for 51Cr compounds by using petroleum ether extraction, gel filtration, cation and anion exchange chromatography and thin layer chromatography. Similar analytical procedures as for the above analysis were used for studying 51Cr compounds formed in the spent culture medium and in a sterile medium. Several 51Cr fractions were isolated from the three chromium sources, but one anionic 51Cr fraction present in the yeast and in the spent culture medium was not found in the sterile medium. Molecular weight estimations of the 51Cr fractions by gel filtration chromatography showed that the 51Cr ion exchange fractions contained several 51Cr compounds. The molecular weights of these compounds ranged from 150 to 1000 daltons and the molecular weights of 51Cr compounds separated from the yeast were markedly lower than those of the corresponding ion exchange fractions isolated from the culture medium. By using thin layer chromatography it was possible to isolate 51Cr compounds from the main bulk of ninhydrin active impurities. The polarity of all 51Cr compounds was found to be greater than that of most amino acids. The 51Cr compounds isolated from the yeast were mixed with 125I-insulin and incubated, after which the solution was eluted through Sephadex G-50 gel to test if binding had occurred. Elution peaks of 51Cr and 125I-insulin showed that 51Cr compounds were not bound to the insulin.     

Effect of phenolic compounds on the co-metabolism of citric acid and sugars by Oenococcus oeni from wine

AIMS: The goal of this study was to examine the growth of Oenococcus oeni in the presence of phenolic compounds under wine conditions and to see how these compounds affect bacterial metabolism. METHODS AND RESULTS: Phenolic compounds have been added to a basal medium that simulates the composition of wine. Fifty milligrams per litre or more of phenolic compounds stimulated bacterial growth. Oenococcus oeni seemed to use citric acid and trehalose, if they were present, before glucose and fructose. Citrate was completely exhausted in three days and the yield of acetate was higher when phenolic compounds were present. CONCLUSIONS: Phenolic compounds reduced the rate of sugar consumption and enhanced citric acid consumption, increasing the yield of acetic acid. SIGNIFICANCE AND IMPACT OF THE STUDY: This study allows a better knowledge of co-metabolism of citric acid and sugars by O. oeni in the presence of phenolic compounds of wine.     

Antioxidative activity of some quaternary ammonium salts incorporated into erythrocyte membranes

The antioxidative activity of two series of amphiphilic compounds from a group of quaternary ammonium salts has been investigated. They were so-called bifunctional surfactants synthesized to be used as common pesticides or as antioxidants. The latter application was to be ensured by providing the compounds studied with an antioxidant group. Studies on antioxidative possibilities of those compounds were performed on pig erythrocytes. Due to their hydrophobic parts, they anchor in the erythrocyte membrane and influence the degree of lipid oxidation in the erythrocyte membrane subjected to UV radiation. It was found that compounds of both series decreased the oxidation of the membrane lipids. The inhibition of this oxidation increased with the length of their hydrophobic chains up to fourteen carbon atoms. The compounds of the longest hydrophobic chains showed a somewhat weaker antioxidative activity. Of the two series studied compounds were more effective having bromide ions as counterions. The corresponding compounds of a second series (chlorides) protected erythrocyte significantly weaker against oxidation. The effect of the compounds on fluidity of the erythrocyte membrane has been studied in order to explain the oxidation results. Change in fluidity of the erythrocyte ghost membranes was found also dependent on length of the hydrophobic part of the compounds and was more pronounced in the case of bromide surfactants. The final conclusion is that the compounds studied can be succesfully used as antioxidant agents of good efficacy.     

Arsenic speciation in human urine reference materials using high-performance liquid chromatography with inductively coupled plasma mass spectrometric detection.

Six arsenic compounds including arsenocholine, arsenobetaine, dimethylarsinic acid, methylarsonic acid, arsenous acid and arsenic acid were separated by high-performance liquid chromatography (HPLC) on a Hamilton PRP-X100 anion-exchange column using isocratic elution and detected by inductively coupled plasma mass spectrometry (ICP-MS). This analytical procedure was applied to the speciation of arsenic compounds in human urine. The influence of urine matrix on the separation of arsenic compounds was evaluated and the determination of arsenic compounds was not hampered by the ArCl interference which has often been encountered in ICP-MS. Three human urine reference materials, SRM 2670 normal level, SRM 2670 elevated level and Lyphocheck urine metal control 1, were analyzed with respect to arsenic compounds by HPLC-ICP-MS. The results were found to be in good agreement with the certified total arsenic concentration in the reference materials. Six arsenic compounds were detected. Arsenobetaine was found to be present in all of the investigated human urine reference materials.     

Gastroprotective and ulcer-healing effect of new solidagenone derivatives in human cell cultures

The labdane diterpene solidagenone 1 and its semisynthetic and biotransformation derivatives 2-10 were assessed for gastroprotective and ulcer-healing effect using human epithelial gastric cells (AGS) and human lung fibroblasts (MRC-5). The ability of the compounds to protect the AGS cells against the damage induced by sodium taurocholate (NaT), to stimulate the cellular reduced glutathione (GSH), prostaglandin E(2) content, enhance AGS and MRC-5 cell proliferation and to scavenge superoxide anion in vitro was studied. The cytotoxicity of the compounds was assessed towards MRC-5 fibroblasts and AGS cells. A significant reduction of cell damage after NaT incubation was observed when the AGS cells were pretreated with compounds 2 and 6. Treatment with compounds 4-6, 8 and 9 significantly stimulated the GSH content in AGS cell cultures. None of the studied compounds was active as a superoxide anion scavenger. In AGS cells treated with compounds 1-10, only compound 5 was able to increase prostaglandin content. Concerning the proliferation assays, a significant stimulating effect was observed for compounds 2, 8, 9 on AGS cells and for 5, 7-9 on MRC-5 fibroblasts. Regarding cytotoxicity, solidagenone showed higher toxicity while compounds 4 and 7 were the less toxic. Our results showed that most of the studied compounds act in vitro as gastroprotectors increasing the cellular GSH content. Additionally, some derivatives exhibited in vitro ulcer-healing effect stimulating the cell proliferation.     

New ligand-based approach for the discovery of antitrypanosomal compounds

The antitrypanosomal activity of 10 already synthesized compounds was in silico predicted as well as in vitro and in vivo explored against Trypanosoma cruzi. For the computational study, an approach based on non-stochastic linear fingerprints to the identification of potential antichagasic compounds is introduced. Molecular structures of 66 organic compounds, 28 with antitrypanosomal activity and 38 having other clinical uses, were parameterized by means of the TOMOCOMD-CARDD software. A linear classification function was derived allowing the discrimination between active and inactive compounds with a confidence of 95%. As predicted, seven compounds showed antitrypanosomal activity (%AE>70) against epimastigotic forms of T. cruzi at a concentration of 100mug/mL. After an unspecific cytotoxic assay, three compounds were evaluated against amastigote forms of the parasite. An in vivo test was carried out for one of the studied compounds.     

Protective action of aromatic compounds against cold-shock injuries in boar spermatozoa.

Butylated hydroxytoluene has been known to protect spermatozoa from cold shock injury. To determine whether such protective action is a common property of aromatic compounds, the effect of 14 hydrophobic and 2 hydrophilic aromatic compounds on the protection of boar spermatozoa from cold shock was investigated. The majority of the hydrophobic compounds tested provided protection; the hydrophilic compounds were ineffective. Of the aromatic compounds tested, naphthalene was most effective in reducing the effect of cold shock on motility and acrosomal integrity of boar spermatozoa.     

Anti-inflammatory profile of some synthesized heterocyclic pyridone and pyridine derivatives fused with steroidal structure

We herein report the anti-inflammatory activity of some newly synthesized heterocyclic pyridone and pyridine derivatives fused with steroidal structure. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All compounds, except 3b, 22, and 23, were interestingly less toxic than the reference drug (Prednisolone). Regarding the protection against Carrageenan-induced edema, eight compounds were found to be more potent than Prednisolone. On the other hand, in searching for COX-2 inhibitor, the inhibition of plasma PGE2 for the compounds was determined and four compounds were found to be more potent than the reference drug. The structure assignment of the new compounds was based on chemical and spectroscopic evidence.     

Methanethiosulfonate Derivatives Inhibit Current through the Ryanodine Receptor/Channel

To identify regions of the ryanodine receptor (RyR) important for ion conduction we modified the channel with sulfhydryl-reacting compounds. After addition of methanethiosulfonate (MTS) compounds channel conductance was decreased while other channel properties, including channel regulation by ATP, caffeine, or Ca, were unaffected. The site of action was accessible to the MTS compounds from the cytoplasmic, but not the luminal, side of the channel. In addition, the hydrophilic MTS compounds were only effective when the channel was open, suggesting that the compounds covalently modify the channel from within the water-filled ion conducting pathway. The decrease in channel current amplitude occurred in a step-wise fashion and was irreversible and cumulative over time, eventually leading to the complete block of channel current. However, the time required for each consecutive modification during continuous exposure to the MTS compounds increased, suggesting that successive modification by the MTS compounds is not independent. These results are consistent with the hypothesis that the channel forms a wide vestibule on the cytoplasmic side and contains a much smaller opening on the luminal side. Furthermore, our results indicate that the MTS compounds can serve as functional markers for specific residues of the RyR to be identified in molecular studies.     

Apoptosis induced by niacin-related compounds in K562 cells but not in normal human lymphocytes

In our previous study, we found that niacin-related compounds induced apoptosis in human acute myelomonocytic leukemia cells, HL-60. We have investigated whether these compounds acted as inducers of apoptosis also in various other cell types. In human chronic myelogenous leukemia cells, K562, which are relatively resistant to various inducers of apoptosis, the apoptosis was induced by picolinic acid and dipicolinic acid in about 50% of the cells 5-10 mM via the caspase pathway, but was not at 1 mM. However, isonicotinamide did not induce apoptosis effectively in K562 cells. On the other hand, in normal human quiescent lymphocytes, the apoptosis was not induced by these compounds at the same concentrations. It is suggested that these compounds may induce apoptosis mainly in tumor cells. The change of intracellular peroxide levels was observed in the early phase of apoptosis induced by niacin-related compounds. We expect to make use of niacin-related compounds in the field of medicine.     

植物与手性化合物的对映体选择性相互作用

植物与手性化合物存在着非常密切的联系.一方面,植物分泌、合成的一些手性化合物,如糖甙、酶、萜类化合物、有机酸及植物激素等,在植物的生理生化过程中起着重要的作用;另一方面,人工合成的手性化合物尤其是农药等环境污染物与植物具有对映体选择性相互作用,它们或是选择性地抑制植物的生长和生理过程,或是被植物选择性地吸收和代谢.因此,在开发、生产和使用手性化合物时需要考虑植物与对映体之间的选择性因素;同时,合理利用植物对手性污染物进行环境修复也具有重要意义.本文对植物与手性化合物相互作用中的对映体选择性进行了综述,并对手性污染物的植物修复进行了展望.     

Effect of water and temperature stress on the content of active constituents of Hypericum brasiliense Choisy.

Hypericum brasiliense is a medicinal herb containing several compounds with important pharmacological activity. In this study, we investigated the effects of water stress (waterlogging and drought) and temperature (low and high, constant and alternate) on the content of betulinic acid and phenolic compounds (quercetin, rutin, 1,5-dihydroxyxanthone, isouliginosin B) in this species. In general, the water stress increased the levels of all of the compounds analyzed, particularly some of the phenolic compounds. On the other hand, the responses to alternating temperatures varied according to the compound. The results for plants kept in growth chambers indicated that low light intensity might have influenced the levels of the compounds. There was also a reallocation of carbon, with water-stressed plants showing a reduction in growth while the levels of the compounds increased. In the temperature treatments, such an increase was evident only for the phenolic compounds.     

Identification of autotoxic compounds in fibrous roots of Rehmannia (Rehmannia glutinosa Libosch.)

Rehmannia is a medicinal plant in China. Autotoxicity has been reported to be one of the major problems hindering the consecutive monoculture of Rehmannia. However, potential autotoxins produced by the fibrous roots are less known. In this study, the autotoxicity of these fibrous roots was investigated. Four groups of autotoxic compounds from the aqueous extracts of the fibrous roots were isolated and characterized. The ethyl acetate extracts of these water-soluble compounds were further analyzed and separated into five fractions. Among them, the most autotoxic fraction (Fr 3) was subjected to GC/MS analysis, resulting in 32 identified compounds. Based on literature, nine compounds were selected for testing their autotoxic effects on radicle growth. Seven out of the nine compounds were phenolic, which significantly reduced radicle growth in a concentration-dependent manner. The other two were aliphatic compounds that showed a moderate inhibition effect at three concentrations. Concentration of these compounds in soil samples was determined by HPLC. Furthermore, the autotoxic compounds were also found in the top soil of the commercially cultivated Rehmannia fields. It appears that a close link exists between the autotoxic effects on the seedlings and the compounds extracted from fibrous roots of Rehmannia.     

Effect of Glucose on the Interaction of Hydrophobic Compounds with the Alanine Receptor Field of Bacillus subtilis Spores during Initiation of Germination

Glucose interfered with the inhibitory action of hydrophobic compounds, such as n-octanol, diphenylamine and 2-tert-butylphenol, during L-alanine-initiated germination of Bacillus subtilis spores. The action of glucose on the action of the hydrophobic compounds was not competitive, and the binding affinity of glucose was not essentially affected by the hydrophobic compounds, indicating the presence of separate binding sites for glucose and the hydrophobic compounds. The binding affinity of D-alanine, a competitive inhibitor of L-alanine, was not affected by the hydrophobic compounds, indicating separate binding sites for D-alanine and the hydrophobic compounds. A possible arrangement of the binding sites for glucose and for the hydrophobic compounds in relation to those for L- and D-alanine on the spores is discussed.     

Thiazolidin-4-one and hydrazone derivatives of capric acid as possible anti-inflammatory, analgesic and hydrogen peroxide-scavenging agents

Starting from capric acid, hydrazone and thiazolidin-4-one derivatives have been synthesized in the present investigation. Decanoic acid hydrazide was reacted appropriately to yield hydrazones, which were then cyclized to yield the corresponding thiazolidin-4-ones. The structures of the newly synthesized compounds were confirmed by analytical and spectral methods. Anti-inflammatory, analgesic, and hydrogen peroxide-scavenging activity of the title compounds were evaluated. Among synthesized compounds, 2-hydroxyphenyl thiazolidinone with 44.90% inhibition of inflammation was the most potent anti-inflammatory agent. Similarly, 4-methoxybenzylidine hydrazide with 64.90% inhibition of writhing was observed to be the most potent analgesic agent of the synthesized compounds. All the synthesized compounds exhibited potent hydrogen peroxide-scavenging activity.