Synthesis and biological evaluation of novel C(6) modified baicalein derivatives as antioxidative agents

Baicalein, one of the major flavones, was found to be responsible for the antioxidative activity of the traditional Chinese medicinal herb Huang-Qin ( Scutellaria baicalensis Georgi), which is widely used as an antioxidative, anti-inflammatory, and antitumor agent. The hydroxyl group of the A ring of the baicalein was alkylated at position 6 with terpenoids such as prenyl, geranyl, and farnesyl groups, and their free radical scavenging activities and glutathione (GSH) depletion capacities were examined. Their free radical scavenging activity was measured according to the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(*+)) scavenging method. Baicalein and newly synthesized baicalein derivatives were found to be good free radical scavengers. Flow cytometrical method was employed to measure the intracellular antioxidative activity and GSH depletion capacity of these derivatives in human acute monocytic leukemia cell line (THP-1). It was also found that baicalein and its derivatives could decrease the levels of exogenous cumene hydroperoxide and H2O2 in THP-1 cells. These compounds also could significantly inhibit the intracellular GSH depletion induced by cumene hydroperoxide in THP-1 cells. The production of cumene hydroperoxide-induced Bax, a pro-apoptotic related protein, could also be inhibited by baicalein and its derivatives. These results suggested that baicalein and its derivatives could be beneficial to human health.     

盐胁迫下两种草坪草膜脂过氧化和抗氧化酶比较

Salinity stress is a major factor limiting the growth of turfgrass irrigated with recycled wastewater. The change in lipid peroxidation in terms of malondialdehyde (MDA) content and the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxide (APX) and glutathione reductase (GR) in the shoots and roots of Kentucky bluegrass and tall fescue were investigated under salinity stress. Plants were subjected to 0, 50, 100, 150 and 200 mmol L 1 NaCl for 40 d. The MDA content under salinity stress was lower in tall fescue than in Kentucky bluegrass in both shoots and roots. Activities of SOD in the shoots of both species increased with salinity stress. The activities of CAT and APX decreased in Kentucky bluegrass, but no significant difference in the activities of CAT and APX was observed in tall fescue. The activities of SOD, CAT and APX in the shoots of tall fescue were higher than those in Kentucky bluegrass. In the roots of Kentucky bluegrass, SOD and GR activities increased and CAT and APX activities decreased in comparison with the control. In the roots of tall fescue, salinity increased the activities of SOD, CAT, and APX. These results suggested that tall fescue exhibited a more effective protection mechanism and mitigated oxidative stress and lipid peroxidation by maintaining higher SOD, CAT and APX activities than Kentucky bluegrass.     

Effect of nickel and grafting combination on yield,fruit quality,antioxidative enzyme activities,lipid peroxidation,and mineral composition of tomato

Soil contamination by heavy metals negatively affects crop productivity, besides representing serious threat to human health. Grafting tomato onto appropriate rootstocks may raise Ni tolerance through limiting heavy metal uptake by roots and/or its translocation to the shoot and by detoxification. A greenhouse experiment was conducted to determine the influence of long‐term Ni exposure (0, 25, or 50 µM) on crop productivity, fruit quality, leaf chlorophyll content, fluorescence, electrolyte leakage, catalase (CAT), ascorbate peroxidase (APX), and guaiacol peroxidase (GPX) activities in leaf, proline content, membrane lipid peroxidation, and mineral composition of tomato plants cv. Ikram, either self‐grafted or grafted onto three rootstocks: Black Beauty, Unifort, and Maxifort. Significant reduction in yield was observed in response to an increase in Ni concentration with more detrimental effects at 50 µM Ni. The fruit dry matter and total soluble solids content increased under severe Ni stress. The depression of crop performance under Ni toxicity was attributed to a decrease in leaf pigments (SPAD index), efficiency of PSII, macro‐ and microelements, and increase in lipid peroxidation and membrane damage. Plants grafted onto tomato rootstocks Maxifort and Unifort exhibited higher chlorophyll content, photochemical activity of PSII, antioxidant activity of APX and GPX, lower accumulation of MDA, and a better nutritional status (higher Ca and Fe, and lower Ni) in the leaf tissues in comparison with self‐grafted plants and those grafted onto Black Beauty. Plants grafted onto tomato rootstocks Unifort and especially Maxifort could minimize the nickel toxicity by improving nutritional status and detoxification processes.     

Synthesis of pentasaccharide and heptasaccharide derivatives and their effects on plant growth

Two oligosaccharide derivatives, beta-D-Glcp-(1-6)-beta-D-Glcp-(1-6)-beta-D-Glcp-(1-6)-beta-D-Glcp-(1-4)-alpha-D-ManpOMe (1) and beta-D-Glcp-(1-6)-beta-D-Glcp-(1-6)-beta-D-Glcp-(1-6)-beta-D-Glcp-(1-6)-beta-D-Glcp-(1-6)-beta-D-Glcp-(1-4)-alpha-D-ManpOMe (2), have been synthesized efficiently using a convergent glycosylation strategy of 2 + 3 and 2 + 5. 1,6-Anhydro-beta-D-glucopyranose, which was prepared from cotton pyrolysis, was applied as a key synthon in the synthesis, significantly simplifying the preparation. The bioassay suggested that these two oligosaccharides can both stimulate the growth of maize cultured in liquid medium at a concentration of 3 ppm.     

Synthesis of pyrazole derivatives and their evaluation as photosynthetic electron transport inhibitors

Two series of new pyrazoles, namely six pyrazolo[1,5-a][1,3,5]triazine-2,4-dione and four pyrazolo[1,5-c][1,3,5]thiadiazine-2-one derivatives, were synthesized as potential inhibitors of the photosynthetic electron transport chain at the photosystem II level. The compounds were confirmed by 1H NMR, elemental, and IR analyses. Their biological activity was evaluated in vivo upon both the growth of blue-green algae and the photosynthetic oxygen evolution by eukaryotic algae and in vitro as the ability to interfere with light-driven reduction of ferricyanide by isolated spinach chloroplasts. Some compounds exhibited remarkable inhibitory properties, comparable to those of the reference commercial herbicides lenacil, diuron, and hexazinone. Results suggest that the substitution of triazine with thiadiazine ring may act as amplifier for herbicidal activity.     

Ameliorative influence of sesame lignans on lipid profile and lipid peroxidation in induced diabetic rats

Sesame lignans are working as antioxidants in various physiological functions. In the present study, the antioxidative effect of sesame lignans is examined in chemically induced diabetes mellitus (DM) in rats against lipid profile and lipid peroxidations. DM was induced in four groups of rats by injection of alloxan. The control groups (non-diabetic and diabetic) received a diet containing sunflower oil while the rest of the three experimental diabetic groups received a diet containing 0.25% alpha-tocopherol (D-Toc), 0.5% sesame lignan (D-SL), and 0.25% alpha-tocopherol+0.25% sesame lignan (D-Toc-SL) in sunflower oil for 4 weeks. Lipid profile and lipid peroxidations of plasma, erythrocyte membrane (EM), and liver tissues were measured. The total cholesterol, non-HDL cholesterol, plasma lipid peroxidation, and also LDL-peroxidation decreased, and HDL cholesterol increased significantly (P<0.05) in all the experimental groups as compared to the control diabetic sunflower oil group. The triacylglycerol (TAG) level in plasma decreased significantly in the D-SL and D-Toc-SL groups as compared to control diabetic group. Significant decrease in TAG level was observed in the D-SL group as compared to the D-Toc group. LDL peroxidation also decreased significantly in the D-Toc-SL group as compared to the D-Toc group. EM lipid peroxidation and liver lipid peroxidation decreased significantly in the D-Toc, D-SL, and D-Toc-SL groups as compared to the control diabetic group. Liver TAG level decreased more significantly in the D-SL and D-Toc-SL groups than in the control diabetic group. So, sesame lignans at 0.5% level and sesame lignan + alpha-tocopherol significantly ameliorate the alteration in lipid profile and the adverse free radical generative influence of DM induced by alloxan.     

Synthesis and fungistatic activity of new groups of 2,4-dihydroxythiobenzoyl derivatives against phytopathogenic fungi

Twenty-six compounds, derivatives of amides, hydrazines, hydrazides, hydrazones, and semicarbazides, with a 2,4-dihydroxythiobenzoyl moiety, were synthesized from sulfinyl-bis(2,4-dihydroxythiobenzoyl). The compositions and chemical structures of these compounds were confirmed by IR, (1)H NMR, EI-MS, and elemental analysis. Antifungal properties of chemicals under in vitro conditions against five phytopathogenic fungi were estimated. In vivo studies against Erisiphe graminis were also carried out. The compounds N-substituted with an 2,4-dihydroxythiobenzamide group proved to be the most active. N-2-(1-Cinnamylbenzene ester)-2,4-dihydroxythiobenzamide, under in vitro conditions, showed activity at the level of 80-100% development of most pathogens at a concentration of 20 microg/mL and partially at a concentration of 200 microg/mL. For compounds with -HN-NH- or -NH-N= moiety, weak or no fungistatic properties were found at the concentrations studied.     

Accumulation of cadmium in growing peanut (Arachis hypogaea L.) seedlings—Its effect on lipid peroxidation and on the antioxidative enzymes catalase and guaiacol peroxidase

In plants exposed to high metal concentrations, mechanisms to counteract the oxidative burst are crucial for its survival. To investigate the temporal sequence of physiological reactions of peanut seedlings (Arachis hypogaea L.) to cadmium exposure, seeds were cultured in increasing concentrations of CdCl₂, ranging from 50 to 300 μM. Germination frequency was scored, and the distributions of Cd in root, stem, and leaves were determined after 2 and 4 weeks of culture. Lipid peroxidation and activities of antioxidative enzymes including catalase (CAT; EC 1.11.1.6) and guaiacol peroxidase (GPX; EC 1.11.1.7) were estimated in these three parts of the plant. Germination of seedlings was not affected, but the growth of seedlings was severely suppressed with increasing concentrations of CdCl₂ and incubation period. Pattern of Cd distribution in the three organs varied with concentration and period of exposure to Cd. Increased lipid peroxidation was detected in all parts of the developing seedlings with increasing metal accumulation. Catalase and guaiacol peroxidase activity varied in the three parts of the seedlings with concentration of Cd and incubation period. Guaiacol peroxidase activity appears to be more active in scavenging the reactive oxygen species in developing peanut seedlings. The results of the present experiment demonstrate the advantages of a tissue‐culture model system in studying the complex network of interactions of various factors in stress tolerance.     

Convenient synthesis of hydroxytyrosol and its lipophilic derivatives from tyrosol or homovanillyl alcohol

Hydroxytyrosol, a naturally occurred o-phenolic compound exhibiting antioxidant properties, was synthesized by a three-step high-yielding procedure from natural and low-cost compounds such as tyrosol or homovanillyl alcohol. First, the efficient chemoselective protection of the alcoholic group of these compounds was performed by using dimethyl carbonate (DMC) as reagent/solvent; second, the oxidation with 2-iodoxybenzoic acid (IBX) or Dess-Martin periodinane reagent (DMP) and in situ reduction with sodium dithionite (Na2S2O4) allowed the preparation of carboxymethylated hydroxytyrosol; finally, by a mild hydrolytic step, hydroxytyrosol was obtained in high yield and purity, as confirmed by NMR spectra and HPLC profile. By using a similar methodology, lipophilic hydroxytyrosol derivatives, utilized as additives in pharmaceutical, food, and cosmetic preparations, were prepared. In fact, at first the chemoselective protection of the alcoholic group of tyrosol and homovanillyl alcohol was performed by using acyl chlorides without any catalyst to obtain the corresponding lipophilic derivatives, and then these compounds were converted in good yield and high purity into the hydroxytyrosol derivatives by oxidative/reductive pathway with IBX or DMP and Na2S2O4.     

Synthesis and insecticidal activity of novel carbamate derivatives as potential dual-binding site acetylcholinesterase inhibitors

In biological systems, bivalent ligands often possess increased functional affinity for their receptors compared with monovalent ligands. On the basis of the structure of acetylcholinesterase (AChE), a series of novel carbamate heterodimetic derivatives were designed and synthesized with the aim of increasing the potency toward AChE inhibition. The AChE inhibitory ability of all the novel compounds was tested using AChE obtained from the brain of the housefly. The bioassay results showed that compounds 6j, 6k, 6m, 6n, 6p, and 6q had increased inhibitory activities in comparison with parent phenyl N-methylcarbamate (MH) at the concentration of 100 mg/L. Among them, the most potent AChE inhibitor of these compounds was 6q (IC(50) = 12 μM), which showed 62-fold greater AChE inhibitory activity than that of MH and 12-fold greater activity than metolcarb (MT), which suggested that the 3-nitrophenoxy moiety of compound 6q was able to interact with the aromatic amino acid residues lining the gorge and the phenyl N-methylcarbamate moiety was able to interact with the catalytic sites of AChE, simultaneously. The insecticidal activities of compounds 6j, 6k, 6m, 6n, 6p, and 6q were further evaluated. Consistent with the result in vitro bioassay, those compounds demonstrated better activities against Lipaphis erysimi than parent compound MH at the concentration of 300 mg/L, and compound 6q showed the best insecticidal activity, causing 98% mortality after 24 h of treatment.     

Inhibition of lipid peroxidation by Lactobacillus acidophilus and Bifidobacterium longum.

The inhibition of lipid peroxidation by Lactobacillus acidophilus and Bifidobacterium longum was investigated using two lipid model systems. All eight strains, including six strains of L. acidophilus and two strains of B. longum, demonstrated an inhibitory effect on linoleic acid peroxidation. The inhibitory rates on linoleic acid peroxidation ranged from 33 to 46% when 1 mL of intracellular cell-free extract was tested. In the second model system, the cell membrane of osteoblast was used as the source for biological lipid. The results indicated that all strains were able to protect biological lipids from oxidation. The inhibition rates on cell membrane lipid peroxidation ranged from 22 to 37%. The effect of L. acidophilus and B. longum on inhibition of fluorescent tissue pigment accumulation was also obtained for osteoblastic cells. The inhibition rates on fluorescent tissue pigment accumulation ranged from 20 to 39%. The antioxidative effect of each milliliter of intracellular cell-free extract of L. acidophilus and B. longum was equivalent to 104-172 ppm of butylated hydroxytoluene (BHT). These results indicated that all strains demonstrated high antioxidative activity. The scavenging ability of lipid peroxidation products, tert-butyl hydroperoxide and malondialdehyde, was also evaluated. The results showed that L. acidophilus and B. longum were not able to scavenge the tert-butyl hydroperoxide. Nevertheless, malondialdehyde was scavenged well by these strains.     

Assessment of radical scavenging capacity and lipid peroxidation inhibiting capacity of antioxidant

The role of radical scavenging antioxidants against oxidative stress has received much attention, and the antioxidant capacity has been assessed by various methods. Among them, a method that measures the effect of antioxidant on decay of the probe is one of the most widely used methods. The present study was performed to compare the two methods to assess the antioxidant capacity, one to follow the decay of the probe and the other to measure lipid peroxidation products in human plasma. It was shown that the method following probe decay was suitable for assessment of radical scavenging capacity of antioxidant, but not for the capacity to inhibit lipid peroxidation in plasma. This is true whether a hydrophilic or lipophilic probe is used. Such different results arise from the fact that the efficacy of inhibition of lipid peroxidation by antioxidants depends on the fate of antioxidant-derived radical and interaction between antioxidants as well as the capacity of free radical scavenging. Thus, the capacity of antioxidants for inhibition of lipid peroxidation should be assessed from the effect on the extent of oxidation, not from the effect on probe decay.     

Effects of hydrophilic and lipophilic beta-sitosterol derivatives on cholesterol absorption and plasma cholesterol levels in rats

The effects of two phytosterol derivatives of beta-sitosterol, a lipophilic derivative (LPSS) and a hydrophilic derivative (HPSS), on cholesterol uptake and blood lipoprotein levels in rats were compared with those of beta-sitosterol. LPSS and HPSS have solubilities of up to 0.05 g/mL in edible oil and 0.15 g/mL in water at 25 degrees C, respectively. The intragastric administration of either 30 or 50 mg of phytosterols with 10 mg of [4- (14)C]-cholesterol per kg of body weight once a day for 3 consecutive days reduced cholesterol uptake by approximately 30% compared to controls that received cholesterol alone. Feeding a cholesterol-enriched diet containing 1% or 3% beta-sitosterol, LPSS, or HPSS for 2 and 4 weeks resulted in lowered levels of total blood cholesterol and reduced the atherogenic index in all groups. These results indicate that LPSS and HPSS have comparable effects to beta-sitosterol in lowering blood cholesterol levels but they differ from beta-sitosterol in having a solubility advantage.     

Regulative actions of dietary soy isoflavone on biological antioxidative system and lipid metabolism in rats

Male Sprague-Dawley rats, 4 weeks of age, were fed purified diets either with or without 0.2% soy isoflavones rich powder for 5 weeks to elucidate their direct functions such as antioxidative action and regulation of lipid metabolism. Dietary soy isoflavones decreased serum lipid peroxide level in rats. Levels of liver and serum alpha-tocopherol were higher in the rats fed isoflavone than in those fed isoflavones-free diet. Thus, dietary soy isoflavones exhibited mild antioxidative function in this animal experiment. Isoflavone metabolites from diet may act as scavengers of reactive oxygen species. Dietary soy isoflavones lowered hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity, although liver cholesterol level was not modulated. However, the levels of serum cholesterol and triglyceride decreased by consumption of soy isoflavones. Therefore, dietary soy isoflavones may exhibit hypocholesterolemic and hypolipidemic functions. Moreover, dietary soy isoflavones lowered hepatic Delta6 desaturase activity. Reflecting this observation, Delta6 desaturation indices ((18:2(n = 6) + 18:3(n = 6))/20:4(n = 6)) of tissue lipids tended to be lower in rats fed isoflavones than in those fed isoflavones-free diet. This action may contribute to the prevention of inflammatory response by imbalance of eicosanoids. These observations suggest that the positive intake of soy isoflavones may reduce the risk of some cardiovasucular diseases through their radical scavenging function and hypocholesterolemic action.     

Oxymyoglobin oxidation and membranal lipid peroxidation initiated by iron redox cycle.

Oxymyoglobin is the main pigment in muscle tissues, responsible for the bright red color of fresh meat. Oxidation of the heme iron from the ferrous to the ferric metmyoglobin produces the brownish color that consumers find undesirable in fresh meat. The aim of this study was to elucidate the mechanism of oxymyoglobin oxidation in muscle tissues by using a model system containing oxymyoglobin and muscle membranes oxidized by an iron redox cycle. Oxidation of oxymyoglobin was determined from the decrease in absorption of the solution measured by a spectrophotometer at 582 nm. Lipid peroxidation was determined by accumulation of TBARS and conjugated dienes. The higher rates of oxidation of oxymyoglobin (20 microM) and lipid oxidation were achieved by using ferric iron and ascorbic acid at concentrations of 50 and 200 microM, respectively. Increasing the concentration of ascorbic acid to 2000 microM switched its effect to antioxidative. Increasing the concentration of oxymyoglobin from 20 to 80 microM inhibited lipid peroxidation by >90% and partially prevented oxymyoglobin oxidation.     

Gallic esters of sucrose as efficient radical scavengers in lipid peroxidation

Three tests of increasing complexity were used to assess the antioxidant activity of five synthetic gallic esters of sucrose bearing 3, 6, 7, or 8 galloyl units. In addition, two of these compounds had 1 or 2 hydrocarbon (C10-C12) acyl chains. Reaction with the DPPH radical led to the evaluation of the number of radicals trapped per galloyl unit n (3-4), as well as the apparent second-order rate constant for H atom donation k (1200-1500/M/s). These results indicated similar contribution and reactivity of all the galloyl units. Inhibition of the AAPH-initiated peroxidation of linoleic acid in a micellar medium confirmed the additive contribution of the galloyl units, whereas the presence of the hydrocarbon acyl chains had no influence. These results suggest an inhibition of initiation at high antioxidant levels and an underlying prooxidant effect of the galloyl radicals at low concentrations. Finally, LDL peroxidation was inhibited in proportion to the number of galloyl units, in agreement with the preceding tests.     

Quercetin-4'-glucoside is more potent than quercetin-3-glucoside in protection of rat intestinal mucosa homogenates against iron ion-induced lipid peroxidation

Quercetin is a typical antioxidative flavonoid found in vegetables, which is more commonly present as its glucosides, quercetin-3-glucoside (Q3G) and quercetin-4'-glucoside (Q4'G). The main aim of this study was to estimate the antioxidant activity of Q3G and Q4'G on iron ion-driven lipid peroxidation of the gastrointestinal mucosa. Q4'G markedly suppressed the lipid peroxidation when rat gastrointestinal mucosa homogenates were incubated with Fe(NO3)3 and ascorbic acid. Its effectiveness was greater as compared to that of Q3G and comparable to that of quercetin aglycone. Furthermore, Q4'G yielded higher amounts of quercetin aglycone than Q3G on incubation with the homogenates. However, Q4'G showed a lower chelating activity in comparison to Q3G. These results indicate that Q4'G, even though it has a low chelating activity, because of its efficient conversion to antioxidative aglycone on exposure to the mucosa, can act as a powerful antioxidant on iron ion driven lipid peroxidation in the intestinal mucosa. Thus, vegetables rich in Q4'G, such as onion, are likely to serve as favorable antioxidant sources for suppressing iron-induced oxidative stress in the intestinal tract.     

Synthesis and biological activity evaluation of 1,2,3-thiadiazole derivatives as potential elicitors with highly systemic acquired resistance

Elicitors provide a broad spectrum of systemic acquired resistance by altering the physical and physiological status of the host plants and, therefore, are among the most successful directions in modern pesticide development for plant protection. To develop a novel elicitor with highly systemic acquired resistance, two series of thiazole- and oxadiazole-containing thiadiazole derivatives were rationally designed and synthesized according to the principle of combination of bioactive substructures in this work. Their structures were characterized by (1)H nuclear magnetic resonance (NMR), infrared (IR), high-resolution mass spectrometry (HRMS), or elemental analysis. Their potential systemic acquired resistance as an elicitor was also evaluated; bioassay results indicated that, among the 23 compounds synthesized, three compounds, 10a, 10d, and 12b, displayed better systemic acquired resistance than the positive control, tiadinil, a commercialized 1,2,3-thiadiazole-based elicitor. In addition, three other compounds, 10f, 12c, and 12j, exhibited a certain degree of fungus growth inhibition in vitro or in vivo. Our results demonstrated that, in combination of bioactive substructures is an interesting exploration for novel pesticide development, thiazole- and oxadiazole-containing thiadiazole derivatives are potential elicitors with good systemic acquired resistance.     

Isolation of novel glucosides related to gingerdiol from ginger and their antioxidative activities

Two novel glucosides of 6-gingerdiol were isolated from fresh ginger (Zingiber officinale Roscoe). Their structures were determined as 1-(4-O-beta-D-glucopyranosyl-3-methoxyphenyl)-3,5-dihydroxydecane (1) and 5-O-beta-D-glucopyranosyl-3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)deca ne (2) by HRFAB-MS and NMR analyses, and the absolute configurations of both aglycons were identified as (3S,5S) by a comparison with synthetic compounds. After incubating these glucosides with acetone powder prepared from fresh ginger, they were confirmed to have been hydrolyzed to 6-gingerdiol by HPLC. This result suggests that these glucosides are the precursors or intermediates of 6-gingerdiol. To recognize their function, their antioxidative activities were investigated and compared to that of their aglycon, 6-gingerdiol, by a linoleic acid model system and by their DPPH radical-scavenging ability. Although 1 did not indicate any activity, 2 had as strong activity as the aglycon in both measurements.     

Synthesis and antifungal activity of novel bisdithiocarbamate derivatives of carbohydrates against Fusarium oxysporum f. sp. lini

Novel carbamic esters possessing a carbohydrate moiety derived from glycerol or D-glucose with two N,N-diethyldithiocarbamoyl groups and a series of bisdithiocarbamic esters having a ketone or an alkyl ester have been synthesized. The in vitro activity of these new compounds was evaluated against Fusarium oxysporum f. sp. lini. Some of the compounds [bis[1,3-S-(N,N-diethyldithiocarbamoyl)]-1, 3-dideoxyglycerol) and diethyl N,N'-(1,3-dideoxyglycer-1, 3-diyl)bis(dithiocarbamate)] were more active for inhibiting vegetative mycelium growth than, respectively, the commercial N, N-diethyldithiocarbamic acid sodium salt and Maneb. The structure activity of these new compounds is discussed.