The effect of complexation with cyclodextrins on the antioxidant and antimicrobial activity of ellagic acid

Purpose: The aim of the paper was to develop the simple procedures for preparation of inclusion complexes of ellagic acid (EA) with cyclodextrins (CDs) and to investigate their antioxidant and antimicrobial activity.

Methods: The structural characterization was carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and nuclear magnetic resonance (NMR) methods. The phase solubility technique was used to investigate the interactions between ‘host’ and ‘guest’ molecules and to estimate the molar ratio between them. The antioxidant and antimicrobial activity of EA and inclusion complexes were determined.

Results: The apparent stability constants were found to be 117?dm³ mol^?1 for the complex with β-CD and 161?dm³ mol^?1 for the complex with (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD). The results of phase-solubility studies showed that EA formed the inclusion complexes with CDs in the molar ratio of 1:1. The calculated half-maximal inhibitory concentration was 41.18?μg cm^?3 for butyl hydroxy toluene, 1.96?μg cm^?3 for EA, 0.88?μg cm^?3 for inclusion complex with HP-β-CD, and 1.27?μg cm^?3 for inclusion complex with β-CD.

Conclusion: The stability constants indicated the rapid release of EA from the inclusion complexes in the aqueous medium at 25?°C. The antioxidant activity of EA was increased, while the antimicrobial activity was preserved after complexation with CDs.     

走马胎中新的岩白菜素衍生物的提取分离及体外抗氧化活性测定

目的研究走马胎(Ardisia gigantifoliaStapf.)的化学成分,采用DPPH法考察化合物的体外抗氧化活性。方法采用多种柱色谱法进行分离纯化,根据理化性质及IR、NMR、ESI-MS等光谱数据进行结构鉴定。采用DPPH自由基清除法对分离得到的化合物进行体外抗氧化活性评价。结果分离得到4个化合物,分别鉴定为:(+)-8-O-(3′,5′)-二甲氧基没食子酰基岩白菜素[(+)-3,4,10-trihydroxy-2-(hydroxymethyl)-9-methoxy-6-oxo-2,3,4,4 a,6,10 b-hexahydropyrano[3,2-c]isochromen-8-yl 4-hydroxy-3,5-dimethoxy benzoate,1]、(-)-岩白菜素[(-)-bergenin,2]、没食子酸(gallic acid,3)、(-)-表儿茶素[(-)-epicatechin,4]。结论化合物1为未见文献报道的新化合物,化合物3、4为首次从走马胎中分离得到。化合物3、4具有一定的抗氧化活性。     

New benzoic acid derivatives from Cassia italica growing in Saudi Arabia and their antioxidant activity

Two new benzoic acid derivatives: 1-p-hydroxy benzoyl-3-palmitoyl glycerol (1) and 6 -p-hydroxy benzoyl daucosterol (2), along with scutellarein-6-methyl ether (3), quercetin (4), and rutin (5) had been separated from Cassia italica (Fabaceae) aerial parts from EtOAc fraction. Their characterisation was accomplished by various spectroscopic techniques and by comparing with the published data. The Ethyl acetate (EtOAc) fraction and compounds 1–5 had been assessed for their antioxidant potential utilizing DPPH assay. They had significant antioxidant capacities with activity ranged from 19.7 to 95.8%, in comparison to butylated hydroxyanisole (BHA) (93.8%). These findings could provide a further evidence to support the traditional use of C. italica for the treatment of chronic or degenerative illnesses.     

New camptothecin and ellagic acid analogues from the root bark of Camptotheca acuminata

As part of a study on chemical constituents of Camptotheca species, one new natural camptothecin analogue (2), two new alkaloids (3, 4), one new ellagic acid analogue (5), and 19 known compounds (1, 6-23) have been isolated from the root bark, stem bark, fruits, and leaves of Camptotheca acuminata Decaisne. The structures of 2-5 were determined from spectral data to be 10-methoxy-20-O-acetylcamptothecin (2), 20-O-beta-glucopyranosyl 18-hydroxycamptothecin (3), 20-formylbenz indolizino [1,2-b]quino-line-11(13H)-one (4), and 3,4-methylenedioxy-3'-O-methyl-5'-hydroxyellagic acid (5).     

Influence of ellagic acid on antioxidant defense system and lipid peroxidation in mice

Addition of ellagic acid (EA) to liver microsomes of mice resulted in a steady increase in inhibition of NADPH-dependent lipid peroxidation up to 2 mM concentration. The maximum of 70% inhibition of ascorbate-dependent lipid peroxidation was achieved at 1 mM concentration of EA. Feeding of EA significantly increased the levels of reduced glutathione and glutathione reductase in liver and lungs of male and female mice. However, there were no changes in the activities of catalase and superoxide dismutase. On the other hand, microsomes from liver and lungs of EA fed animals showed significantly suppressed NADPH- and ascorbate-dependent lipid peroxidation.     

Chitosan derivatives with antimicrobial, antitumour and antioxidant activities--a review

Chitosan is a linear polysaccharide with a good biodegradability, biocompatibility, and no toxicity, which provide it with huge potential for future development. The chitosan molecule appears to be a suitable polymeric complex for many biomedical applications. This review gathers current findings on the antibacterial, antifungal, antitumour and antioxidant activities of chitosan derivatives and concurs with our previous review presenting data collected up to 2008. Antibacterial activity is based on molecular weight, the degree of deacetylation, the type of substitutents, which can be cationic or easily form cations, and the type of bacterium. In general, high molecular weight chitosan cannot pass through cell membranes and forms a film that protects cells against nutrient transport through the microbial cell membrane. Low molecular weight chitosan derivatives are water soluble and can better incorporate the active molecule into the cell. Gram-negative bacteria, often represented by Escherichia coli, have an anionic bacterial surface on which cationic chitosan derivatives interact electrostatically. Thus, many chitosan conjugates have cationic components such as ammonium, pyridinium or piperazinium substituents introduced into their molecules to increase their positive charge. Gram-positive bacteria like Staphylococcus aureus are inhibited by the binding of lower molecular weight chitosan derivatives to DNA or RNA. Chitosan nanoparticles exhibit an increase in loading capacity and efficacy. Antitumour active compounds such as doxorubicin, paclitaxel, docetaxel and norcantharidin are used as drug carriers. It is evident that chitosan, with its low molecular weight, is a useful carrier for molecular drugs requiring targeted delivery. The antioxidant scavenging activity of chitosan has been established by the strong hydrogen-donating ability of chitosan. The low molecular weight and greater degree of quarternization have a positive influence on the antioxidant activity of chitosan. Phenolic and polyphenolic compounds with antioxidant effects are condensed with chitosan to form mutual prodrugs.     

Bile acid derivatives with antimicrobial activity

A series of condensation products of cholic and dehydrocholic acids with (L)-aminoacids was prepared and tested in vitro for antimicrobial activity. The derivatives of cholic acid with basic aminoacids showed significant activity, especially marked when (L)-arginine was the condensed aminoacid.     

Synthesis and antimicrobial activity of hydroxy-isophthalaldehyde acid derivatives

4-hydroxy-isophthalaldehyde acid (1), its alkyl esters (methyl, ethyl, propyl and butyl) and alkyl ethers (propyl, butyl, pentyl and esyl), as well as 6-hydroxy-isophthalaldehyde acid (2) ita alkyl esters (methyl and ethyl), 4-hydroxy-5-iodo-isophthalaldehyde acid (3) and its methyl ester were synthesized and characterized. Antimicrobial and antifungal activity was tested and the LD50 of the most active compound 4 was determined.     

Antioxidant and antimicrobial activities of cinnamic acid derivatives

Cinnamic acid is an organic acid occurring naturally in plants that has low toxicity and a broad spectrum of biological activities. In the search for novel pharmacologically active compounds, cinnamic acid derivatives are important and promising compounds with high potential for development into drugs. Many cinnamic acid derivatives, especially those with the phenolic hydroxyl group, are well-known antioxidants and are supposed to have several health benefits due to their strong free radical scavenging properties. It is also well known that cinnamic acid has antimicrobial activity. Cinnamic acid derivatives, both isolated from plant material and synthesized, have been reported to have antibacterial, antiviral and antifungal properties. Acids, esters, amides, hydrazides and related derivatives of cinnamic acid with such activities are here reviewed.     

Novel indolyl-pyrimidine derivatives: synthesis,antimicrobial, and antioxidant evaluations

In the present study, a novel series of indolyl-pyrimidines (1–13) were synthesized starting from 4-hydrazinopyrimidine-5-carbonitrile 3. Elemental analysis, IR, ¹H-NMR, ¹³C-NMR, and mass spectral data elucidated structure of newly synthesized compounds. All compounds were screened for their in vitro antibacterial, antifungal, and some for antioxidant activities. Compounds 5, 9g, 9i, and 9j showed pronounced antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Escherichia coli, Candida albicans, and Aspergillus flavus compared to the reference drugs, while compounds 3 and 9g displayed promising free radical scavenging activity and found to be more potent than standard, ascorbic acid (vitamin C). Further, some compounds were evaluated for cytotoxic activity by SRB assay method against human colon carcinoma (CaCo-2) and showed that compounds 4 and 9g were found to be the highly active compared to the reference drug doxorubicin. Their structure and activity relationship were discussed.     

秀丽莓中鞣花酸的含量测定和抗氧化活性评测及对接研究

目的建立秀丽莓中鞣花酸的含量测定方法并对其抗氧化活性进行研究。方法采用RP-HPLC法,SunFireTMC18色谱柱(150mm×4.6mm,5μm),乙腈-4mL·L-1磷酸水(20∶80)为流动相;流速:1.0mL·min-1;检测波长:254nm;柱温:35℃。有机结合计算机分子模拟及体外DPPH·抗氧化活性评价方法对其可能的作用机制及活性进行深入探讨。结果鞣花酸的线性范围为0.081 92~0.409 60μg(r=0.999 7,n=6);平均回收率(n=6)为99.51%(RSD=2.00%)。该成分可通过结构中的酚羟基经氢键、苯环经π-π键作用与受体蛋白的氨基结合起效,具有较维生素C更强的抗氧化活性。结论该方法可迅速、准确地测定秀丽莓中的鞣花酸含量,可作为该药材中主要抗氧化成分鞣花酸质量控制和评价的有效方法,为该药材的进一步开发提供判断方法。     

Isolation, purification and identification of ellagic acid derivatives, catechins, and procyanidins from the root bark of Anisophyllea dichostyla R. Br.

The root bark of Anisophyllea dichostyla R. Br. is traditionally used in the Democratic Republic Congo for the treatment of several conditions such as anorexia, fatigue and intestinal infections. We have identified and quantitated several polyphenol antioxidants in the methanol extract of the root bark (120g). The polyphenol content (3.32g/kg) was predominantly ellagitannins (25%) and polyhydroxyflavan-3-ols (catechins and procyanidins, 75%) with 3'-O-methyl-3,4-methylenedioxo ellagic acid 4'-O-beta-d-glucopyranoside and (-)-epicatechin as the major species in each class. These two compounds and the following species were identified unequivocally by NMR spectroscopy: (+)-catechin, (-)-epicatechin 3-O-gallate, 3-O-methyl ellagic acid, 3,3'-di-O-methyl ellagic acid, 3'-O-methyl-3,4-methylenedioxo ellagic acid, 3'-O-methyl-3,4-methylenedioxo ellagic acid 4'-O-beta-d-glucopyranoside, and 3'-O-methyl ellagic acid 4-O-beta-d-xylopyranoside. The following additional compounds were purified by semi-preparative HPLC and tentatively identified on the basis of UV spectra, HPLC-ESI-MS and nano-ESI-MS-MS: (+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin (procyanidin B(1)), epicatechin-(4beta-->8)-epicatechin (procyanidin B(2)), an (epi)catechin trimer, 3-O-methyl ellagic acid 4-O-beta-d-glucopyranoside, (-)-epicatechin 3-O-vanillate, 3,4-methylenedioxo ellagic acid 4'-O- beta-d-glucopyranoside, and 3,3'-di-O-methyl ellagic acid 4-O-beta-d-xylopyranoside. Fractionation of the raw extract by column chromatography on silicic acid yielded 10 fractions. In the hypoxanthine/xanthine oxidase antioxidant assay system, CC-9 which contained a range of polyphenols dominated by (-)-epicatechin-O-gallate proved to be the most potent antioxidant fraction (IC(50)=52 micro g/mL) in terms of ROS scavenging. In terms of XO inhibition CC-8, dominated by (epi)catechin trimer and which also contained appreciable amounts of 3'-O-methyl ellagic acid 4'-O-beta-d-xylopyranoside, as well as the catechins (+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin (procyanidin B(1)), and (-)-epicatechin 3-O-gallate, proved to be the most potent (IC(50)=36 micro g/mL).     

New pyridine derivatives as potential antimicrobial agents

A set of pyridine derivatives bearing a substituted alkylthio chain or a piperidyl ring in position 2 or 4 were synthesized, and their antimycobacterial and antifugal activities were evaluated. Chemical structures were confirmed by IR and NMR data, and by elemental analysis. Minimum inhibitory concentrations (MIC) were used for the evaluation of microbiological activity in vitro. The compounds were moderately active against both Mycobacterium tuberculosis and nontuberculous mycobacteria. The most active compound was 2-cyanomethylthiopyridine-4-carbonitrile (7) with MIC against Mycobacterium kansasii in the range of 8-4 mumol/l. The antifungal activities of the compounds were relatively low.     

Two new ellagic acid rhamnosides from Punica granatum heartwood

From Punica granatum heartwood two new ellagic acid rhamnosides, 3- O-methylellagic acid 4-O-alpha-L-rhamnopyranoside (1) and 3,4'-O-dimethylellagic acid 4-O-alpha-L-rhamnopyranoside (2) were isolated together with brevifolincarboxylic acid, 3-O-methylellagic acid and 4,4'-O-dimethylellagic acid.     

Synthesis of new olefin chalcone derivatives as antitumor, antioxidant and antimicrobial agents

Chalcone is a unique template that is associated with several biological activities. Claisen–Schmidt condensation of olefin aldehyde 3 and various mono, disubstituted and heterocyclic acetophenones afforded novel olefin chalcones. Synthesized compounds were subjected for ADME prediction by computational method which revealed that these molecules can be considered as a potential drug. Out of the 21 compounds screened, compounds 5u, 5g, 5c and 5e have shown significant cytotoxicity against Hep 3BPN 7, compounds 5j, 5i, 5n and 5o showed good cytotoxicity against HL 60 P 58. Compounds 5f, 5c, 5e and 5b showed potent cytotoxicity against Hela B 75. Antioxidant activity was assessed using three methods, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical scavenging and ferric reducing antioxidant power (FRAP). The result shows that all these compounds possess significant antioxidant activity. Compounds 5k, 5s, 5a and 5c showed promising antibacterial activity. Compounds 5k, 5u and 5f could be considered as chemopreventive agents.     

Arylidenepyruvic acid thiosemicarbazone and thiazoline derivatives as potential antimicrobial agents

Two novel series of arylidenepyruvic acid thiosemicarbazone and thiazoline derivatives were synthesized and evaluated as potential antimicrobial agents. These substances did not exhibit any significant antibacterial effects when tested against a variety of microorganisms.     

Synthesis,antimicrobial, and antioxidant activity of benzofuran barbitone and benzofuran thiobarbitone derivatives

The synthesis of novel series of benzofuran derivatives, containing barbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl) methylidene]pyrimidin-2,4,6(1H,3H,5H)-trione (4a–i) and thiobarbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl)methylidene]-2-thioxodihydropyrimidin-4,6(1H, 5H)-dione (5a–i) have been reported. The target compounds (4a–i) and (5a–i) were synthesized by the Knoevenagel condensation of (5-substituted-1-benzofuran-2-yl)(2/4-substitutedphenyl) methanone (3a–i) with barbituric acid and thiobarbituric acid, respectively, in acid medium. These compounds were screened for the antimicrobial and antioxidant activities. From antimicrobial activity results it was found that compounds 4a, 5a, 4c, and 5c displayed good antibacterial and antifungal activity against all tested strains. Further, the synthesized compounds were studied for docking on the enzyme, Glucosamine-6-phosphate synthase and the compounds 4c and 5c have emerged has an active antimicrobial agent with least binding energy (?5.27 and ?4.85 kJ mol^?1). Compounds 4e, 4f, 5e, and 5f showed promising free radical scavenging activity and compounds 5a and 5b showed good chelating ability with Fe²⁺ ions.     

Synthesis and antimicrobial and antioxidant activities of simple saccharin derivatives with N-basic side chains

A new class of N-basic side chains was obtained from 2,3-dihydro-2H-3-oxobenzo[d]isothiazole and aliphatic or aromatic aldehydes. Secondary amines (morpholine, N-methylpiperazine and ethyl isonipecotate) afforded tertiary N-basic side chains (4–6), while dibasic secondary amines (such as piperazine) gave bis-tertiary N-basic side chains (2). On the other hand, the use of mono- or dibasic primary amines namely; aniline, anisidine, phenyl hydrazine, o-hydroxy benzoic acid hydrazide, hydrazine hydrate, and ethylenediamine (instead of secondary amines) afforded secondary N-basic side chain as mono component or as bis component 7a-c, 9a-c, 11 and 12a-c. In addition, secondary Mannich base was synthesized via Michael addition to the corresponding aldimine. The new compounds were investigated for antioxidant and antimicrobial activities. Compounds 2, 7c and 12a exhibited significant antimicrobial activity, whereas compounds 7a, 7b, 9b, 9c and 11 exhibited high antioxidant activity as compared to ascorbic acid, These compounds showed the best protective effect against DNA damage induced by bleomycin.