A new flavone, named crotoncaudatin (1), was isolated from the stems of Croton caudatus Geisel. var. tomentosus Hook., together with nine known analogues: 3,5,6,7,8,3′,4′-heptamethoxyflavone (2), tangeretin (3), nobiletin (4), 5,6,7,4′-tetramethoxy-flavone (5), sinensetin (6), kaempferol (7), tiliroside (8), kaempferol-3-O-rutinoside (9) and rutin (10). The structures of the above compounds were established by a combination of spectroscopic methods, including HR-ESI-MS, ¹H-NMR, ¹³C-NMR, HMQC and HMBC spectra^. All compounds were isolated from and identified in this species for the first time and compounds 1-6 are new for the genus Croton. Full article

Compoundswith two phenolic OH groups like curcumin possess efficient antioxidant and anti-inflammatory activity. We synthesized p-cresol dimer (2,2'-dihydroxy-5,5'-dimethylbiphenol, 2a) and p-methoxyphenol dimer (2,2'-dihydroxy-5,5'-dimethoxybiphenol, 2b) by ortho-ortho coupling reactions of the parent monomers, p-cresol (1a) and p-methoxyphenol (1b), respectively. Their antioxidant activity was determined using the induction period method, and their cytotoxicity towards RAW 264.7 cells was also investigated using a cell counting kit. The stoichiometric factors n (number of free radicals trapped by one mole of antioxidant moiety) for 2a and 2b were 3 and 2.8, respectively, being greater than those for 1a and 1b. The ratio of the rate constant of inhibition to that of propagation (k_inh/k_p) for 2a and 2b was similar to that for 2-t-butyl-4-methoxyphenol (BHA), a conventional food antioxidant. The 50% inhibitory dose (ID₅₀) declined in the order 1b > 1a >> 2b > 2a > BHA. The cytotoxicity for 2a and 2b was significantly greater than that for the parent monomers (p < 0.001), but smaller than that for BHA (p < 0.01). Compounds 2a and 2b may be useful as food antioxidants. Full article

The course of reaction of aryl and heteroaryl sulfonamides with diphenylcarbonate (DPC) and 4-dimethylaminopyridine (DMAP) was found to depend on the pKa of the sulfonamide used. Aryl sulfonamides with pK_a ~ 10 gave 4-dimethylamino-pyridinium arylsulfonyl-carbamoylides, while the more acidic heteroaryl sulfonamides (pK_a ~ 8) furnished 4-dimethylaminopyridinium heteroarylsulfonyl carbamates. Both the carbamoylides and carbamate salts reacted with aliphatic and aromatic amines with the formation of appropriate aryl(heteroaryl)sulfonyl ureas, and therefore, can be regarded as safe and stable substitutes of the hazardous and difficult to handle aryl(heteroaryl)sulfonyl isocyanates. Full article

We have selected aptamers binding to lysozyme from a DNA library using capillary electrophoresis-systematic evolution of ligands by exponential enrichment. During the selection process the dissociation constant of the ssDNA pool decreased from the micromolar to the low nanomolar range within five rounds of selection. The final aptamer had a dissociation constant of 2.8 ± 0.3 nM, 6.1 ± 0.5 nM, and 52.9 ± 9.1 nM as determined by fluorescence anisotropy, surface plasmon resonance and affinity capillary electrophoresis respectively. The aptamers were successfully challenged for specificity against other egg white proteins. The high affinity aptamers open up possibilities for the development of aptamer based food and medical diagnostics. Full article

Yan73 is a “teinturier” red wine variety cultivated in China and used in winemaking to strengthen red wine color. Here, the anthocyanin profile in both the skin and pulp of this grape variety was analyzed by HPLC-MS. The results showed that 18 anthocyanins were detected in both the skin and the pulp, and pelargonidin-3-O-glucoside, an anthocyanin compound hardly detected in most other Vitis viniferaberries, was found. However, the contents of individual anthocyanins in the skin and the pulp were significantly different. Compared with the skin, the pulp exhibited much lower ratio of 3’,5’-substituted to 3’-substituted anthocyanins and much higher ratio of methoxylation of anthocyanin B-ring to non methoxylation, and with regard to the aromatic acylated and aliphatic acylated anthocyanins, both their contents in the skin are higher than in the pulp. The findings will provide some new insight for the tissue-specific expression and regulation of the genes involving in anthocyanin biosynthesis in grape berries. Full article

A new geldanamycin analogue was isolated from Streptomyces hygroscopicus A070101. The structure was elucidated as 11-methoxy-17-formyl-17-demethoxy-18-O-21-O-dihydrogeldanamycin (1) on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis. Compound 1 showed considerable cytotoxicity (SRB) against human cancer cell lines (breast cancer MCF-7, skin melanoma SK-MEL-2 and lung carcinoma COR-L23). Full article

The association constants K_b of three hosts I–III designed to have both enhanced hydrogen bonding donor strength and conformational preorganization with biotin analogues 1–5 are reported. ¹H-NMR titrations under two different concentration conditions have been employed to determine the association constants K_b. A statistical analysis using a presence absence matrix has been applied to calculate the different contributions. Hydrogen bond interactions make naphthyridine derivatives II and III potent binders and effective receptors for (+)-biotin methyl ester (1), due to the complex stabilization by additional hydrogen bonds. Full article

The in vitro antiradical activity of Schisandra chinensis lignans was investigated using DPPH, ABTS⁺, Fenton reaction inhibition and tyrosine-nitration inhibition assays, as were the in vivo antidiabetic activities of selected lignans in an animal model of alloxan-induced diabetes. Different degrees of antiradical activity were found, depending upon the structural parameters of the tested compounds. Unfortunately, the compounds showed no antidiabetic activity in concentration range tested. Full article

Research over the past decade has indicated that melanocortin peptides are potent inhibitors of inflammation and a promising source of new anti-inflammatory and cytoprotective therapies. The purpose of the present paper is to compare protective effects of α-, β-, and γ-melanocyte stimulating hormone on acetaminophen induced liver lesions in male CBA mice. Acetaminophen was applied intragastrically in a dose of 150 mg/kg, and tested substances were applied intraperitoneally 1 hour before acetaminophen. Mice were sacrificed after 24 hours and intensity of liver injury was estimated by measurement of plasma transaminase activity (AST and ALT) and histopathological grading of lesions. It was found that α-, β-, and γ-MSH decrease intensity of lesions by both criteria in a dose-dependent manner. Full article

Both bifidobacteria and clostridia are part of the natural gut microflora and while clostridia may be responsible for severe intestinal infections, bifidobacteria are probiotic microorganisms belonging to the most important prospective bacteria in the bowel. The antimicrobial activity of biochanin A was tested in vitro against six Bifidobacterium spp., and eight Clostridium spp. using the broth microdilution method. Biochanin A showed an inhibition against all clostridia in the range of minimum inhibitory concentrations (MIC) from 64 μg/mL (for Cl. clostridioforme, strains DSM 933 and I3) to 1,024 μg/mL (for Cl. perfringens, DSM 11778). No bifidobacteria were suppressed at four-fold higher concentration (MICs > 4,096) than MIC of Cl. perfringens. These results indicate selective growth inhibition of biochanin A and its potential use in antimicrobial prevention and/or protection. Full article

A catalytic asymmetric nitro-Mannich (aza-Henry) reaction with rare earth metal/alkali metal heterobimetallic catalysts is described. A Yb/K heterobimetallic catalyst assembled by an amide-based ligand promoted the asymmetric nitro-Mannich reaction to afford enantioenriched anti-b-nitroamines in up to 86% ee. Facile reduction of the nitro functionality allowed for efficient access to optically active 1,2-diamines. Full article

The reduction of γ-N-benzylamino-β-ketophosphonates 6 and 10, readily available from L-proline and L-serine, respectively, can be carried out in high diastereoselectivity with catecholborane (CB) in THF at -78 ºC to produce the syn-γ-N-benzylamino-β-hydroxyphosphonates 11 and 13 as a single detectable diastereoisomer, under non-chelation or Felkin-Anh model control. Full article

A series of Ru(II) and Os(II) tris-chelate complexes with new bidentate 2-pyridylquinoline ligands have been synthesized and fully characterized by EA,¹H-NMR and FAB-MS techniques. The new ligands are: L₁ = 4-p-methoxyphenyl-6-bromo-2-(2′- pyridyl)quinoline (mphbr-pq) and L₂ = 4-p-hydroxyphenyl-6-bromo-2-(2′-pyridyl)-quinoline (hphbr-pq). The complexes studied are: [Ru(bpy)₂L₁](PF₆)₂ (C₁), [Ru(bpy)₂L₂](PF₆)₂ (C₂), [Os(bpy)₂L₁](PF₆)₂ (C₃), [Os(bpy)₂L₂](PF₆)₂ (C₄) (bpy = 2,2′-bipyridine), [Ru(dmbpy)₂L₁](PF₆)₂ (C₅), [Ru(dmbpy)₂L₂](PF₆)₂ (C₆), [Os(dmbpy)₂L₁](PF₆)₂ (C₇), and [Os(dmbpy)₂L₂](PF₆)₂ (C₈) (dmbpy = 4,4′-dimethyl-2,2′-bipyridine). Moreover, new functionalized complexes C₉-C₁₂ were obtained by the basecatalyzed direct alkylation of C₂, C₄, C₆, and C₈ with 6-bromo-1-hexene. The complete assignment of the ¹H-NMR spectra for the two new ligands (L₁ and L₂), and their Ru(II) or Os(II) complexes has been accomplished using a combination of one- and two-dimensional NMR techniques. The J_H,H values have been determined for the majority of the resonances. Full article

A novel method for the conversion of unprotected and unmodified aldoses to aldo-imidazoles has been developed. Using iodine as a catalyst in acetic acid solution, a series of mono- and oligosaccharides, including those containing carboxyl and acetamido groups, undergo an oxidative condensation reaction with aromatic vicinal diamines at room temperature to give the corresponding aldo-imidazole products in high yields. No cleavage of the glycosidic bond occurs under the mild reaction conditions. The compositional analysis of saccharides is commonly realized by capillary electropheresis of the corresponding aldo-imidazole derivatives, which are easily synthesized by the reported iodine-promoted oxidative condensation. In addition, a series of aldo-imidazoles were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI–TOF MS) to analyze molecular weight and ion intensity. The diamine-labeled saccharides showed enhanced signals in MALDI–TOF MS. The combined use of aldoimidazole derivatization and mass spectrometric analysis thus provides a rapid method for identification of saccharides, even when less than 1 pmol of saccharide is present in the sample. These results can be further applied to facilitate the isolation and analysis of novel saccharides. Full article

The cationic ring-opening polymerization reaction of tetrahydrofuran at 20 ºC was catalyzed by H₃PW₁₂O₄₀·13H₂O as solid acid catalyst. The effect of the proportions of acetic anhydride and catalyst, reaction time and support on the polymerization reaction was investigated. It has been found that the yield and the viscosity of the polymer depend on the proportion of acetic anhydride, the presence of the latter in the reactant mixture being required for the ring-opening. The catalytic activity of the alumina-supported heteropolyacid results showed that Brønsted acid sites are more effective than Lewis ones for the cationic ring-opening polymerization. Full article

SrCl₂·6H₂O has been shown to act as an efficient catalyst for the conversion of aldehydes or ketones into the corresponding gem-dihydroperoxides (DHPs) by treatment with aqueous H₂O₂ (30%) in acetonitrile. The reactions proceed under mild and neutral conditions at room temperature to afford good to excellent yields of product. Full article

A novel chiral macrocyclic ligand incorporating a chiral salen moiety into a framework containing two biphenyl units was synthesized. Structural properties and conformational aspects of the free ligand and an UO₂ complex were studied by using NMR spectroscopy in solution and MM calculations. The Mn(III) complex was tested as catalyst in enantioselective oxidation of prochiral unfunctionalized olefins to the corresponding optically active epoxides under very mild conditions. Full article

Nephelium lappaceum is a tropical fruit whose peel possesses antioxidant properties. Experiments on the isolation and identification of the active constituents were conducted, and on their antioxidant activity using a lipid peroxidation inhibition assay. The methanolic extract of N. lappaceum peels exhibited strong antioxidant properties. Sephadex LH-20 chromatography was utilized in the isolation of each constituent and the antioxidant properties of each was studied. The isolated compounds were identified as ellagic acid (EA) (1), corilagin (2) and geraniin (3). These compounds accounted for 69.3% of methanolic extract, with geraniin (56.8%) as the major component, and exhibited much greater antioxidant activities than BHT in both lipid peroxidation (77-186 fold) and DPPH^• (42-87 fold) assays. The results suggest that the isolated ellagitannins, as the principal components of rambutan peels, could be further utilized as both a medicine and in the food industry. Full article

The oxidation of 1-unsubstituted or 1-phenyl-1H-isotellurochromenes with m-chloroperbenzoic acid (mCPBA) in CHCl₃ resulted in a ring opening reaction to produce as the sole products the corresponding o-formyl or benzoyl distyryl ditellurides, which were also produced by the hydrolysis of the 2-benzotelluropyrylium salts readily prepared from the parent isotellurochromene. Full article

Coprinus comatus, also called chicken drumstick mushroom, is currently commercially available in China. Hot water and ethanolic extracts were prepared from cap and stipe of C. comatus fruit bodies and their antioxidant properties were studied. Ethanolic extract from stipe showed high antioxidant activity (80.6%) at 1 mg/mL. Reducing power of hot water extracts from cap was 1.653 at 10 mg/mL. Extracts from cap showed better scavenging ability on DPPH (57.9% at 1 mg/mL) than stipe ones. Ethanolic extracts were more effective in scavenging ability on hydroxyl radicals (57.4–61.3% at 5 mg/mL) than hot water extracts. Ethanolic extracts showed moderate scavenging ability on superoxide radicals (46.3–47.0% at 20 mg/mL). Naturally occurring antioxidant components including total phenols (3.60–20.00 mg/g), tocopherols (0.58–11.93 mg/g), flavonoids (0.19–3.52 mg/g) and polysaccharides (58.52–547.86 mg/g) were found in the extracts. Overall, extracts from cap were more effective for the antioxidant properties assayed. Full article

The thermal [4+2] cycloadditions of 3-acetyl-, 3-carbamoyl, and 3-ethoxycarbonylcoumarins with 2,3-dimethyl-1,3-butadiene under solvent free conditions are reported, as well as the epoxidation reactions of some adducts. Discussion is focused on the structural features of the Diels-Alder adducts and their epoxides, based upon NMR, X-ray, and mass spectral data, and supported by ab initio theoretical calculations. Full article

We have identified through bioassay guided isolation an allelochemical, eudesmane-type sesquiterpeniod, 3β-caffeoxyl-β1,8α-dihydroxyeudesm-4(15)-ene(1),from an endemic plant species growing in the Himalayas. In our search for the bioactive subfraction, the hexane one was highly significant, showing 100% inhibition of lettuce seed growth at 100 ppm while other subfractions (chloroform, ethyl acetate, butanol and water) exhibited inhibitory to stimulatory allelopathic effects. The bioactive hexane subfraction was subjected to chromatographic techniques, using lettuce seeds (Lactuca sativa) as indicator species to reveal the bioactive allelopathic fraction. This resulted in the isolation of compound 1, whose structure was elucidated through NMR techniques. The compound presented 92.34% inhibitory effect on the growth of lettuce at 500 ppm. Further field level experiments may help develop an environmentally friendly herbicide from this lead. Full article

Complexes between oxovanadium (IV) cation and flavonoid derivatives were developed recently in order to increase the intestinal absorption and to reduce the toxicity of vanadium compounds. For these reasons, is interesting to investigate the complexation process between flavonoid rutin (Rut) and vanadyl cation in order to isolate new complexes. Two new complexes [VO(Rut)(H₂O)₂](SO₄)_0.5×2H₂O and [VO(Rut)₂]×4H₂O have been obtained and characterized by elemental and thermal analyses and several spectroscopic techniques (ESI-MS, IR, UV-Vis, fluorescence). The studies concerning complex formation between vanadyl and rutin (Rut) performed in different solutions show the formation of mononuclear complexes with 1:1 and 1:2 metal to ligand stoichiometry. Full article

Combinatorial chemistry is a powerful tool used to rapidly generate a large number of potentially biologically active compounds. In our goal to develop bisubstrate inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) that interact with both the substrate (estrone or estradiol) and the cofactor (NAD(P)H) binding sites, we used parallel solid-phase synthesis to prepare three libraries of 16β-estradiol derivatives with two or three levels of molecular diversity. From estrone, we first synthesized a sulfamate precursor that we loaded on trityl chloride resin using the efficient multidetachable sulfamate linker strategy recently developed in our laboratory. We then introduced molecular diversity [one or two amino acid(s) followed by a carboxylic acid] on steroid nucleus by Fmoc peptide chemistry. Finally, after a nucleophilic cleavage, libraries of 30, 63 and 25 estradiol derivatives were provided. A library of 30 sulfamoylated estradiol derivatives was also generated by acidic cleavage and its members were screened for inhibition of steroid sulfatase. Biological evaluation on homogenated HEK-293 cells overexpressing 17β-HSD1 of the estradiol derivatives carrying different oligoamide-type chains at C-16 first revealed that three levels of molecular diversity (a spacer of two amino acids) were necessary to interact with the adenosine part of the cofactor binding site. Second, the best inhibition was obtained when hydrophobic residues (phenylalanine) were used as building blocks. Full article

Folic acid plays an important role in neuronal development. A series of newly synthesized bioactive compounds (NSCs) was reported to exhibit immunoactive and neuroprotective functions. The isolated and combined effects of folic acid and NSCs against β-amyloid (Aβ)-induced cytotoxicity are poorly understood. These effects were tested using human microglia cells (C13NJ) subjected to Aβ_(25-35) challenge. According to an MTT assay, treatment of C13NJ cells with Aβ_(25-35) at 10~100 μM for 48 h induced 18%~43% cellular death in a dose-dependent manner (p < 0.05). Aβ_(25-35) treatment at 25 μM induced nitrite oxide (NO) release, elevated superoxide production, and reduced the distribution of cells in the S phase. Preincubation of C13NJ with 100 μM folic acid protected against Aβ_(25-35)-induced cell death, which coincided with a reduction in NO release by folic acid supplements. NSC47 at a level of 50 μM protected against Aβ_(25-35)-induced cell death and reduced Aβ-promoted superoxide production (p < 0.05). Folic acid in combination with NSC47 at their cytoprotective doses did not synergistically ameliorate Aβ_(25-35)-associated NO release, superoxide production, or cell cycle arrest. Taken together, folic acid or NSC treatment alone, but not the combined regimen, protected against Aβ_(25-35)-induced cell death, which may partially, if not completely, be mediated by free radical-scavenging effects. Full article

We instituted a quasi-quality assurance program for demonstrating coniferyl alcohol’s fluorescence and fluorescence diminishment following enzymatic oxidation. The magnitude of diminishment was a measure of catalysis. High throughput screening was performed in pseudo-kinetic and endpoint modes by measuring the fluorescence at 416 nm following excitation at 290, 310 or 340 nm. Dose-response tracings were linear between two and three orders of magnitude with average limits of detection and quantitation of 1.8 and 6.9 mM coniferyl alcohol, respectively. Oxidation was evident with 0.025 mg/mL laccase or 0.003 mg/mL peroxidase or inside 5 min using 0.5 mg/mL laccase or 5 mM substrate. Sodium chloride inhibited (IC₅₀, 25 mM) laccase oxidation of coniferyl alcohol. Fluorescence from 10 concentrations (1 to 1000 mM) of coniferyl alcohol was stable for 24 hours over 14 excitation/emission cycles at 3 different combinations of excitation and emission wavelengths. In conclusion, coniferyl alcohol absorption and fluorescence assays should facilitate biomass lignin analyses and improve delignification. Full article

Investigations were carried out to determine antimicrobial and antioxidant properties and total phenol content of three wild species of Ephedra compared with their respective callus cultures. Callus induction was performed in a standard Murashige and Skoog (MS) medium with the following hormonal ranges (mg/L) for every species NAA:1.5, Kin:1 for Ephedra strobiliacea, NAA:2, Kin:1 for Ephedra procera and NAA:2, Kin:0.5 for Ephedra pachyclada. These ranges of PGPR (Plant Growth Promote Regulators) were chosen based on callus induction rates, RGR (Relative Growth Rate) and their fresh weights. An antimicrobial test against five Gram negative and two Gram positive bacteria and two fungi was performed using the disc diffusion method. All methanolic extracts showed antimicrobial activity, but the antimicrobial activity of the callus cultures was lower than those of the wild plants. E. strobilacea showed the highest antimicrobial activity, and all methanolic extracts of the wild plants and callus cultures unexpectedly showed the highest antimicrobial activity against Pseudomonas aeruginosa. A FRAP (Ferric Reducing Antioxidant Power) test was conducted to evaluate extracts for antioxidant activity. E. strobilacea with 1.61 ± 0.08 mmol eq quercetin/gextract and 0.278 ± 0.02 mmol eq quercetin/gextract for the wild plant and callus, respectively, showed the highest results.The total phenol content of extracts was measured by a Folin Ciocalteau test. All the chosen species displayed phenol contents but E. strobilacea had the highest amount (504.9 ± 41.51 μmol eq catechin/gextracts and 114.61 ± 15.13 μmol eq catechin/gextracts for the wild plants and callus, respectively). Full article

In this study we investigated the antimicrobial activity of magnolol on Staphylococcus aureus. The minimal inhibitory concentrations of magnolol against 31 S. aureus strains ranged from 4–32 μg/mL. In addition, hemolysin assays, Western blotting, and real-time RT-PCR were performed to investigate the effect of magnolol on α-toxin secretion by both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The results indicated that sub-inhibitory concentrations of magnolol dose-dependently inhibited the transcription of hla (the gene encoding α-toxin) in S. aureus, resulting in a reduction of α-toxin secretion and, thus, hemolytic activities. Full article

West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors. Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals are urgently needed. We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. A primary screen of a 13,001 compound library at a 10 µM final concentration was conducted using the 384-well format. Z′ values ranged from 0.54–0.83 with a median of 0.74. Average S/B was 17 and S/N for each plate ranged from 10.8 to 23.9. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. Seven compounds showed potential as small molecule probes directed at WNV. The hit rate from the primary screen was 0.185% (24 compounds out of 13,001 compounds) and from the secondary screens was 0.053% (7 out of 13,001 compounds) respectively. Full article

Organotin monomers containing dibutyltin groups – dibutyltin citraconate (DBTC) as a new monomer and dibutyltin maleate (DBTM) – were synthesized. Free radical copolymerizations of the organotin monomers with styrene (ST) and butyl acrylate (BA) were performed. The overall conversion was kept low (≤15% wt/wt) for all studied samples and the copolymers composition was determined from tin analysis using the Gillman and Rosenberg method. The reactivity ratios were calculated from the copolymer composition using the Fineman-Ross (FR) method. The synthesized monomers were characterized by elemental analysis, 1H-, 13C-NMR and FTIR spectroscopy. Full article

A new macromolecule possessing two dansyl moieties and based on 2-[4-(2-aminoethylthio)butylthio]ethanamine was prepared as a fluorescent sensor and its mercury sensing properties toward various transition metal, alkali, and alkali earth ions were investigated. The designed compound exhibited pronounced Hg²⁺-selective ON-OFF type fluorescence switching upon binding. The new compoundprovided highly selective sensing to Hg²⁺ in acetonitrile-water solvent mixtures with a detection limit of 2.49 x 10^{-7 M or 50 ppb.} The molecular modeling results indicated that ions-recognition of the sensor originated from a self assembly process of the reagentand Hg²⁺ to form a helical wrapping structure with the favorable electrostatic interactions of Hg²⁺coordinated with sulfur, oxygen, nitrogen atoms and aromatic moieties. Full article

Antimicrobial activity and cytotoxicity of fifty one extracts of different parts of 14 plants were studied. Ethanol, methanol, aqueous, butanol, and n-hexane extracts were tested against three Gram negative, two Gram positive bacteria, and two fungi. Cytotoxicity and phytochemical screening were determined using MTT and TLC assays, respectively. Of the fifty one extracts, twenty two showed activities against different microorganisms with MICs ranging from 62.5 to 1000 µg/mL. The highest activity (100% inhibition) was for a butanol extract of Rosa damascena receptacles against Salmonella typhimurium and Bacillus cereus (MIC of 62.5 and 250 µg/mL) respectively. Butanol extract of Narcissus tazetta aerial parts and aqueous extract of Rosa damascena receptacles were both active against Candida albicans (MIC of 125 µg/mL). Methicillin-resistant Staphylococcus aureus was inhibited by butanol, aqueous extracts of Rosa damascena receptacles and butanol extract of Inula viscosa flowers (MIC of 500, 500, and 250 µg/mL) respectively. Rosa damascena receptacles and Verbascum sinaiticum flowers ethanol extract showed lowest cytoxicity against Vero cell line (IC₅₀ of 454.11and 367.11). Most toxic was the ethanol extract of Ononis hirta aerial parts (IC₅₀ 72.50 µg/mL). Flavonoids and terpenoids were present in all plants. Ononis hirta and Narcissus tazetta contained alkaloids. The results validate the use of these plants and report for the first time bioactivity of Rosa damascena receptacles and further justifies the use of such screening programs in the quest for new drugs. Full article

A new triterpenoid saponin was isolated from Pulsatilla cernua, along with eight known triterpenoids and triterpenoid glycosides. The new compound was identified as 3-O-β-D-glucopyranosyl-(1→4)-α-L-arabinopyranosyl-bayogenin-28-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (1) on the basis of 1D, 2D-NMR techniques, including COSY, HMBC, and HMQC correlations, MS analysis, as well as chemical methods. Full article

The focus of this paper was to identify a cheaper solvent from among diesel fuel, kerosene, sulfolane or a mixture of sulfolane and cyclohexanol for the preparation of cyanuric acid heterocyclization of urea. To obtain a higher yield, the effects of catalyst (sodium, ammonium, calcium and zinc salts) and temperature (160 °C to 220 °C) on the trimerization of urea were also carefully studied. We established the optimal reaction conditions and further validated them in our scale-up experiments. Full article

In this manuscript, we report clear evidence for the generation of aromatic cation radicals produced by using [hydroxy(tosyloxy)iodo]benzene (HTIB) in fluoroalcohol solvents such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). The single-electron-transfer (SET) oxidation ability of HTIB to give cation radicals was first established by ESR and UV measurements. The reaction was broadly applied to various thiophenes, and unique thienyliodonium salts were directly synthesized by this method in excellent yields without the production of any harmful byproducts. Full article

Using a cell-based cytotoxicity assay three new cytotoxic azaphilones, including two stereoisomers and designated monapurones A-C (1-3), were isolated from the extract of Monascus purpureus-fermented rice (red yeast rice). Their structures were elucidated by detailed interpretation of spectroscopic and chemical data. The relative configurations were assigned on the basis of analysis of NOE data, and the absolute configurations were determined by direct comparison of their CD spectra with those of known azaphilones and chemical correlations. In the in vitro assays, monapurones A-C (1-3) showed selective cytotoxicity against human cancer cell line A549 with IC₅₀ values of 3.8, 2.8 and 2.4mM respectively, while exhibiting no significant toxicity to normal MRC-5 and WI-38 cells at the same concentration. Full article

Quaternary pyridinium salts with chains ranging from C₈ to C₂₀ belong in the large group of cationic surfactants. In this paper, the preparation of such cationic surface active agents based on the pyridinium moiety and differing in the length of the N-alkyl chain is described. Additionally, HPLC technique was established to distinguish each prepared pyridinium analogue. This study represents universal method for preparation and identification of quaternary pyridinium detergents. Full article

Conjugate addition reaction of various nucleophiles across the vinyl group of 2-chloro-4-vinylpyrimidine, 2-chloro-4-(1-phenylvinyl)pyrimidine and 2-chloro-4-vinylquinazoline provides the corresponding 2-chloro-4-(2-substituted ethyl)pyrimidines and 2-chloro-4-(2-substituted ethyl)quinazolines. Treatment of these products, without isolation, with N-methylpiperazine results in nucleophilic displacement of chloride and yields the corresponding 2,4-disubstituted pyrimidines and quinazolines. Full article

Isoflavones are a class of bioactive polyphenols with cancer chemopreventive properties. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a naturally occurring antitumor agent that selectively induces programmed death (apoptosis) in cancer cells. Polyphenols can modulate TRAIL-mediated apoptosis in cancer cells. We examined the cytotoxic and apoptotic activities of isoflavones in combination with TRAIL on HeLa cancer cells. The apoptosis was detected by fluorescence microscopy with annexin V-FITC. The cytotoxicity was evaluated by MTT and LDH assays. The tested isoflavones: genistein, biochanin-A and neobavaisoflavone enhance TRAIL-induced apoptosis in HeLa cells. Our study indicated that isoflavones augmented TRAIL-cytotoxicity against cancer cells and confirmed potential role of those polyphenols in chemoprevention. Full article

The biologically active compounds in wine, especially phenolics, are responsible for reduced risk of developing chronic diseases (cardiovascular disrease, cancer, diabetes, etc.), due to their antioxidant activities. We determined the contents of total phenolics (TP) and total flavonoids (TF) in selected Serbian white wines by colorimetric methods. Total antioxidant activity (TAA) of the white wines was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity assay. Međaš beli had the highest content of TP, TF and TAA. The radical scavenging capacity (RSC) and total antioxidant activity (TAA) of white wines were 15.30% and 1.055 mM Trolox equivalent, respectively. Total phenolic (TP) and total flavonoid (TF) contents in white wines ranged from 238.3 to 420.6 mg gallic acid equivalent per L of wines and 42.64 to 81.32 mg catechin equivalent per L of wines, respectively. A high and significant correlation between antioxidant activity and total phenolic content was determined in wines (R² = 0.968, p < 0.01). For the individual polyphenols determination we used a high performance liquid chromatography (HPLC)-diode array detection (DAD) technique. The majority of white wine polyphenols was represent by four hydroxycinnamic acids (HCAs). Full article

This study reports the synthesis and antioxidant activity of some new acetamide derivatives. The compounds’ structures were elucidated by NMR analysis and their melting points were measured. The in vitro antioxidant activity of these compounds was tested by evaluating the amount of scavenged ABTS radical and estimating ROS and NO production in tBOH- or LPS-stimulated J774.A1 macrophages. All compounds were tested for their effect on cell viability by an MTT assay and by a Brine Shrimp Test. Full article

Novel heteroleptic iridium complexes containing the 1-substituted-4-phenyl-1H-1,2,3-triazole (phtl) cyclometalating ligand have been synthesized. The 3+2 Huisgen dipolar cycloaddition method (‘click’ chemistry) was utilized to prepare a class of bidentate ligands (phtl) bearing different substituents on the triazole moiety. By using various ligands (phtl-R₁ and pytl-R₂) (R₁=adamantane, methyl and R₂=adamantane, methyl, β-cyclodextrin, ursodeoxycholic acid), we prepared a small library of new luminescent ionic iridium complexes [Ir(phtr-R₁)₂(pytl-R₂)]Cl and report on their photophysical properties. The flexibility of the clicking approach allows a straightforward control on the chemical-physical properties of the complexes by varying the nature of the substituent on the ligand. Full article

Both acute and chronic degenerative diseases of the nervous system reduce the viability and function of neurons through changes in intracellular calcium signaling. In particular, pathological increases in the intracellular calcium concentration promote such pathogenesis. Disease involvement of numerous regulators of intracellular calcium signaling located on the plasma membrane and intracellular organelles has been documented. Diverse groups of chemical compounds targeting ion channels, G-protein coupled receptors, pumps and enzymes have been identified as potential neuroprotectants. The present review summarizes the discovery, mechanisms and biological activity of neuroprotective molecules targeting proteins that control intracellular calcium signaling to preserve or restore structure and function of the nervous system. Disease relevance, clinical applications and new technologies for the identification of such molecules are being discussed. Full article

Epidemiological evidence indicates that nutritionally-derived polyphenols such as resveratrol (RES) have neuroprotective properties. Administration of RES to culture media protects a wide variety of neuronal cell types from stress-induced death. Dietary supplementation of RES can ameliorate neuronal damage and death resulting from both acute and chronic stresses in rodents. The specific molecular mechanisms by which RES acts at the cellular level remain incompletely understood. However, many experimental data indicate that RES reduces or prevents the occurrence of oxidative damage. Here we discuss possible mechanisms by which RES might exert protection against oxidative damage and cell death. Evidence suggesting that RES’s chemical antioxidant potential is not sufficient explanation for its effects is discussed. Putative biological activities, including interactions with estrogen receptors and sirtuins are critically discussed. We provide a synthesis of how RES’s phytoestrogenic properties might mediate the neuronal stress resistance underlying its observed neuroprotective properties. Full article

Reduced glutathione (GSH) is the most abundant non-protein thiol in mammalian cells and the preferred substrate for several enzymes in xenobiotic metabolism and antioxidant defense. It plays an important role in many cellular processes, such as cell differentiation, proliferation and apoptosis. GSH deficiency has been observed in aging and in a wide range of pathologies, including neurodegenerative disorders and cystic fibrosis (CF), as well as in several viral infections. Use of GSH as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. Several reports have provided evidence for the use of GSH prodrugs able to replenish intracellular GSH levels. This review discusses different strategies for increasing GSH levels by supplying reversible bioconjugates able to cross the cellular membrane more easily than GSH and to provide a source of thiols for GSH synthesis. Full article

Since its identification in the early 1970s, artemisinin, as well as semi-synthetic derivatives and synthetic trioxanes, have been used in malaria therapy. Reduction of artemisinin by NaBH₄ produced dihydroartemisinin (DHA), and yielded a new stereochemically labile centre at C-10, which, in turn, provided two interconverting lactol hemiacetal epimers (namely a and b), whose rate of interconversion depends on buffer, pH, and solvent polarity. Since interconversion of the two epimers occurred on a chromatographic time-scale, this prompted a thorough investigation of the phenomenon as a crucial requisite of any analytical method aimed at quantitating this family of drugs. In this critical review we discuss the current importance of the on-column epimerization of DHA in the development of analytical methods aimed at quantifying the drug, with the purpose of identifying the optimal conditions to minimize on-column epimerization while achieving the best selectivity and efficiency of the overall separation. Full article

New synthetic methods for the preparation of biologically active phospholipids and lysophospholipids (LPLs) are very important in solving problems of membrane–chemistry and biochemistry. Traditionally considered just as second-messenger molecules regulating intracellular signalling pathways, LPLs have recently shown to be involved in many physiological and pathological processes such as inflammation, reproduction, angiogenesis, tumorogenesis, atherosclerosis and nervous system regulation. Elucidation of the mechanistic details involved in the enzymological, cell-biological and membrane-biophysical roles of LPLs relies obviously on the availability of structurally diverse compounds. A variety of chemical and enzymatic routes have been reported in the literature for the synthesis of LPLs: the enzymatic transformation of natural glycerophospholipids (GPLs) using regiospecific enzymes such as phospholipases A₁ (PLA₁), A₂ (PLA₂) phospholipase D (PLD) and different lipases, the coupling of enzymatic processes with chemical transformations, the complete chemical synthesis of LPLs starting from glycerol or derivatives. In this review, chemo-enzymatic procedures leading to 1- and 2-LPLs will be described. Full article

Artemisinins have become essential antimalarial drugs for increasingly widespread drug-resistant malaria strains. Although tremendous efforts have been devoted to decipher how this class of molecules works, their exact antimalarial mechanism is still an enigma. Several hypotheses have been proposed to explain their actions, including alkylation of heme by carbon-centered free radicals, interference with proteins such as the sarcoplasmic/endoplasmic calcium ATPase (SERCA), as well as damaging of normal mitochondrial functions. Besides artemisinins, other endoperoxides with various backbones have also been synthesized, some of which showed comparable or even higher antimalarial effects. It is noteworthy that among these artemisinin derivatives, some enantiomers displayed similar in vitro malaria killing efficacy. In this article, the proposed mechanisms of action of artemisinins are reviewed in light of medicinal chemistry findings characterized by efficacy-structure studies, with the hope of gaining more insight into how these potent drugs work. Full article

Development of effective and environmentally friendly disinfectants, or virucidal agents, should help prevent the spread of infectious diseases through human contact with contaminated surfaces. These agents may also be used, if non-toxic to cells and tissues, as chemotherapeutic agents against infectious diseases. We have shown that arginine has a synergistic effect with a variety of virucidal conditions, namely acidic pH and high temperature, on virus inactivation. All of these treatments are effective, however, at the expense of toxicity. The ability of arginine to lower the effective threshold of these parameters may reduce the occurrence of potential toxic side effects. While it is clear that arginine can be safely used, the mechanism of its virus inactivation has not yet been elucidated. Here we examine the damages that viruses suffer from various physical and chemical stresses and their relations to virus inactivation and aggregation. Based on the relationship between the stress-induced structural damages and the infectivity of a virus, we will propose several plausible mechanisms describing the effects of arginine on virus inactivation using the current knowledge of aqueous arginine solution properties. Full article

The direct aerobic coupling reaction of arenes with olefins was successfully achieved by the use of Pd(OAc)₂/molybdovanadophosphoric acid (HPMoV) as a key catalyst under 1 atm of dioxygen. This catalytic system could be extended to the coupling reaction of various substituted benzenes with olefins such as acrylates, aclrolein, and ethylene through the direct aromatic C-H bond activation. Full article

Aerobic and anaerobic respiratory systemsallow cells to transport the electrons to terminal electron acceptors. The quinone (ubiquinone or menaquinone) pool is central to the electron transport chain. In the majority of Gram-positive bacteria, vitamin K₂ (menaquinone) is the sole quinone in the electron transport chain, and thus, the bacterial enzymes catalyzing the synthesis of menaquinone are potential targets for the development of novel antibacterial drugs. This manuscript reviews the role of vitamin K in bacteria and humans, and especially emphasizes on recent aspects of menaquinones in bacterial electron transport chain and on discoveries of inhibitor molecules targeting bacterial electron transport systems for new antibacterial agents. Full article

Inula britannica L., family Asteraceae, is used in traditional Chinese and Kampo Medicines for various diseases. Flowers or the aerial parts are a rich source of secondary metabolites. These consist mainly of terpenoids (sesquiterpene lactones and dimmers, diterpenes and triterpenoids) and flavonoids. The isolated compounds have shown diverse biological activities: anticancer, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective activities. This review provides information on isolated bioactive phytochemicals and pharmacological potentials of I. britannica. Full article

Despite international efforts to ‘roll back malaria’ the 2008 World Malaria Report revealed the disease still affects approximately 3 billion people in 109 countries; 45 within the WHO African region. The latest report however does provide some ‘cautious optimism’; more than one third of malarious countries have documented greater than 50% reductions in malaria cases in 2008 compared to 2000. The goal of the Member States at the World Health Assembly and ‘Roll Back Malaria’ (RBM) partnership is to reduce the numbers of malaria cases and deaths recorded in 2000 by 50% or more by the end of 2010. Although malaria is preventable it is most prevalent in poorer countries where prevention is difficult and prophylaxis is generally not an option. The burden of disease has increased by the emergence of multi drug resistant (MDR) parasites which threatens the use of established and cost effective antimalarial agents. After a major change in treatment policies, artemisinins are now the frontline treatment to aid rapid clearance of parasitaemia and quick resolution of symptoms. Since artemisinin and its derivatives are eliminated rapidly, artemisinin combination therapies (ACT’s) are now recommended to delay resistance mechanisms. In spite of these precautionary measures reduced susceptibility of parasites to the artemisinin-based component of ACT’s has developed at the Thai-Cambodian border, a historical ‘hot spot’ for MDR parasite evolution and emergence. This development raises serious concerns for the future of the artemsinins and this is not helped by controversy related to the mode of action. Although a number of potential targets have been proposed the actual mechanism of action remains ambiguous. Interestingly, artemisinins have also shown potent and broad anticancer properties in cell lines and animal models and are becoming established as anti-schistosomal agents. In this review we will discuss the recent evidence explaining bioactivation and potential molecular targets in the chemotherapy of malaria and cancer. Full article

Despite the poor reputation of electron-deficient pyridazines in intermolecular Hetero Diels-Alder (HDA) reactions, 4,5-dicyanopyridazine (DCP) showed a surprising reactivity as a heterocyclic azadiene in inverse electron-demand HDA processes with different dienophiles. The use of alkenes, alkynes and enamines as 2p electron counterparts afforded dicyanocyclohexa-1,3-dienes and substituted phthalonitriles, respectively, while the use of suitable bis-dienophiles provides a general strategy for the one-pot synthesis of polycyclic carbo- and hetero-cage systemsthrough pericyclic three-step homodomino processes. HDA reactions with heterocyclic dienophiles allowed direct benzoannelation: in particular, pyrrole and indole derivatives were converted to dicyano-indoles and -carbazoles. In addition an unprecedented reactivity of DCP as a very reactive heterocyclic electrophile at the C-4 carbon was also evidenced: by changing the experimental conditions, cyanopyrrolyl- and cyanoindolyl-pyridazines were obtained through reactions of pyrrole and indole systems as carbon nucleophiles in formal S_NAr2 processes where a CN group of DCP acts as leaving group. Thus, careful control of the reaction conditions allows exploitation of both pathways for the synthesis of different classes of heterocyclic derivatives. Full article

Vitamin E is an essential vitamin and a lipid soluble antioxidant, at least, under in vitro conditions. The antioxidant properties of vitamin E are exerted through its phenolic hydroxyl group, which donates hydrogen to peroxyl radicals, resulting in the formation of stable lipid species. Beside an antioxidant role, important cell signalling properties of vitamin E have been described. By using gene chip technology we have identified α-tocopherol sensitive molecular targets in vivo including christmas factor (involved in the blood coagulation) and 5α-steroid reductase type 1 (catalyzes the conversion of testosterone to 5α-dihydrotestosterone) being upregulated and γ-glutamyl-cysteinyl synthetase (the rate limiting enzyme in GSH synthesis) being downregulated due to a-tocopherol deficiency. α-Tocopherol regulates signal transduction cascades not only at the mRNA but also at the miRNA level since miRNA 122a (involved in lipid metabolism) and miRNA 125b (involved in inflammation) are downregulated by α-tocopherol. Genetic polymorphisms may determine the biological and gene-regulatory activity of a-tocopherol. In this context we have recently shown that genes encoding for proteins involved in peripheral α-tocopherol transport and degradation are significantly affected by the apoE genotype. Full article

Prostate cancer (PC) is the second most common cancer in men worldwide. Its prevention and treatment remain a challenge to clinicians. Here we review the relationship of vitamins to PC risk. Many vitamins and related chemicals, including vitamin A, retinoids, several B vitamins, vitamin C, vitamin D and vitamin E have shown their anti-cancer activities as anti-oxidants, activators of transcription factors or factors influencing epigenetic events. Although laboratory tests including the use of animal models showed these vitamins may have anti-PC properties, whether they can effectively prevent the development and/or progression of PC in humans remains to be intensively studied subjects. This review will provide up-to-date information regarding the recent outcomes of laboratory, epidemiology and/or clinical trials on the effects of vitamins on PC prevention and/or treatment. Full article

The role of vitamin A and its metabolites in the life processes starting with the historical background and its up to date information is discussed in the introduction. Also the role of 11Z-retinal in vision and retinoic acid in the biological processes is elucidated. The essential role of isotopically enriched systems in the progress of vision research, nutrition research etc. is discussed. In part B industrial commercial syntheses of vitamin A by the two leading companies Hoffmann-La Roche (now DSM) and BASF are discussed. The knowledge obtained via these pioneering syntheses has been essential for the further synthetic efforts in vitamin A field by other scientific groups. The rest of the paper is devoted to the synthetic efforts of the Leiden group that gives an access to the preparation of site directed high level isotope enrichment in retinals. First the synthesis of the retinals with deuterium incorporation in the conjugated side chain is reviewed. Then, ¹³C-labeled retinals are discussed. This is followed by the discussion of a convergent synthetic scheme that allows a rational access to prepare any isotopomer of retinals. The schemes that provide access to prepare any possible isotope enriched chemically modified systems are discussed. Finally, nor-retinals and bridged retinals that give access to a whole (as yet incomplete) library of possible isotopomers are reviewed. Full article

Many studies indicate that traditional Chinese herbs are beneficial in the prevention and treatment of cardiovascular diseases. Evodia rutaecarpa (‘Wu-Chu-Yu’)remains the most popular and multi-purpose herb traditionally used in China for treatment of headache, abdominal pain, postpartum hemorrhage, dysentery and amenorrhea. Rutaecarpine is one of the intriguing indolopyridoquinazoline alkaloids isolated from ‘Wu-Chu-Yu’. Rutaecarpine has been shown to have cardiovascular biological effects such as inotropic and chronotropic, vasorelaxant, anti-platelet aggregation and anti-inflammatory effects. Furthermore, it has been reported that rutaecarpine has beneficial effects on some cardiovascular diseases. This review summarizes data on the cardiovascular pharmacological actions of rutaecarpine the published over the recent years, aiming to provide more evidence supporting its use in the treatment of cardiovascular diseases. Full article

Lipid vesicles spontaneously fuse and assemble into a lipid bilayer on planar or spherical silica surfaces and other substrates. The supported lipid bilayers (SLBs) maintain characteristics of biological membranes, and are thus considered to be biomembrane mimetic systems that are stable because of the underlying substrate. Examples of their shared characteristics with biomembranes include lateral fluidity, barrier formation to ions and molecules, and their ability to incorporate membrane proteins into them. Biomimetic silica microspheres consisting of SLBs on solid or porous silica microspheres have been utilized for different biosensing applications. The advantages of such biomimetic microspheres for biosensing include their increased surface area to volume ratio which improves the detection limits of analytes, and their amenability for miniaturization, multiplexing and high throughput screening. This review presents examples and formats of using such biomimetic solid or porous silica microspheres in biosensing. Full article

Reproductive toxicity is an important regulatory endpoint, which is required in registration procedures of chemicals used for different purposes (for example pesticides). The in vivo tests are expensive, time consuming and require large numbers of animals, which must be sacrificed. Therefore an effort is ongoing to develop alternative In vitro and in silico methods to evaluate reproductive toxicity. In this review we describe some modeling approaches. In the first example we describe the CAESAR model for prediction of reproductive toxicity; the second example shows a classification model for endocrine disruption potential based on counter propagation artificial neural networks; the third example shows a modeling of relative binding affinity to rat estrogen receptor, and the fourth one shows a receptor dependent modeling experiment. Full article