Molecules, Volume 13, Issue 12 (December 2008) – 26 articles , Pages 2925-3252

We found that dodecatungstophosphoric acid (H₃PW₁₂O₄0), samarium and ruthenium(III) chloride act as efficient catalysts for synthesis of unsaturated 2-phenyl-5(4H)oxazolone derivatives under solvent-free conditions. The key features of the reported protocols are short reaction times, high yields of products, ambient conditions and simple workup. Full article

The oxidative dehydrogenation of dihydroarenes catalyzed by 2,3-dichloro-5,6-dicyano-benzoquinone(DDQ) and NaNO₂ with dioxygen is reported. The combination of DDQ and NaNO₂ showed high efficiency and high selectivity, compared with other benzoquinones and anthraquinones, e.g., >99% conversion of 9,10-dihydroanthracene with 99% selectivity for anthracene can be obtained at 120 °C under 1.3 MPa O₂ for 8 h. Excellent results were achieved in the oxidative dehydrogenation of variety of dihydroarenes. Full article

During the last two decades triterpenes have attracted attention because of their pharmacological potential. Triterpene extract (TE) from outer bark of birch consisting mainly of betulin is able to form an oleogel which was successfully tested in the treatment of actinic keratosis. Some aspects of TE in vitro pharmacology are already known. Now we show preliminary pharmacokinetics of betulin and results of a subchronic toxicity study of TE in rats and dogs. Because of poor aqueous solubility of the TE-triterpenes (< 0.1 μg/mL respectively), for pharmacokinetic studies it was suspended in sesame oil (rats, i.p.) and PEG 400 / 0.9 % NaCl (dogs, s.c.). I.p. administered, betulin, the main component of TE, shows time dependency over a period of 4 h and reaches a dose-independent serum level of 0.13 μg/mL. Dose dependency was observed with s.c. administration. At 300 mg/kg a maximum plasma concentration of 0.33 μg/mL betulin was detected after 28 daily applications. The subchronic toxicity study showed no toxicity of TE in rats (i.p.) and dogs (s.c.). In conclusion, triterpene extract from birch bark is safe, its betulin is bioavailable and in addition to published triterpene biological activities TE provides high potential for further pharmaceutical and pharmacological research. Full article

Peptic ulcer disease is a deep gastrointestinal erosion disorder that involves the entire mucosal thickness and can even penetrate the muscular mucosa. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including this one. These products usually derive from plant and animal sources that contain active constituents such as alkaloids, flavonoids, terpenoids, tannins and others. The alkaloids are natural nitrogen-containing secondary metabolites mostly derived from amino acids and found in about 20% of plants. There has been considerable pharmacological research into the antiulcer activity of these compounds. In this work we review the literature on alkaloids with antiulcer activity, which covers about sixty-one alkaloids, fifty-five of which have activity against this disease when induced in animals. Full article

A general method for the preparation of bis-ureas from bis(o-nitrophenyl) carbonate has been developed. Directional urea synthesis is achieved by sequential amine addition to bis(o-nitrophenyl) carbonate in two steps: in the first step bis(o-nitrophenyl) carbonate is reacted with benzylamine to form benzyl-o-nitrophenyl carbamate; in the second step the carbamate is reacted with a variety of diamines in toluene to yield bis-ureas. Full article

C-Glycosyl-(S)- and (R)-alanines 12a and 12b were synthesized from the known β-C-glycoside 1. The nitrogen function was introduced by aza-Claisen rearrangement of the allylic thiocyanate 7, derived from the corresponding alcohol 6. The absolute configuration of the newly created chiral carbon center (C-3) was assigned by X-ray diffraction analysis of the intermediate 3(S)-isothiocyanato-D-glycero-D-galacto-decose 8a. Full article

The imidazole-4,5-dicarboxylic acid scaffold is readily derivatized with amino acid esters and alkanamines to afford compounds with intramolecularly hydrogen bonded conformations that mimic substituted purines and therefore are hypothesized to be potential inhibitors of kinases through competitive binding to the ATP site. In this work, a total of 126 dissymmetrically disubstituted imidazole-4,5-dicarboxamides with amino acid ester and alkanamide substituents were prepared by parallel synthesis. The library members were purified by column chromatography on silica gel and the purified compounds characterized by LC-MS with LC detection at 214 nm. A selection of the final compounds was also analyzed by ¹H-NMR spectroscopy. The analytically pure final products have been submitted to the Molecular Library Small Molecule Repository (MLSMR) for screening in the Molecular Library Screening Center Network (MLSCN) as part of the NIH Roadmap. Full article

A mild acidic dioxane extraction method was employed to isolate lignin from hardwood bleached chemimechanical pulp (BCMP). The isolated lignin was then purified and undergone elemental analysis. To study the photodegradation behavior, the lignin samples were impregnated onto the Whatman filter papers and irradiated with UV light for various periods. The photolyzed lignin was then recovered and analyzed by ¹H-NMR spectroscopy. Phenylpropane-based formula (C₉) of CMP pulp lignin and the photolyzed samples were then established with elemental analysis and ¹H-NMR spectroscopy data. The results indicated that the benzaldehyde and benzoic acid type compounds were the main photodegradation products of BCMP lignin. The lignin photodegradation probably involved the degradation of phenylcoumaran units. Irradiation also increased the phenolic hydroxyl group content and decreased that of methoxyl groups, due to demethoxylation. The degrees of aromatic ring condensation were increased upon continuing the irradiation time, which imples the formation of condensed structures in photolyzed lignin. Full article

Spectroscopic, viscometric, and molecular docking analysis of binding of cationic bis-porphyrins linked with p- or m-xylylenediamine (H₂pXy and H₂mXy) and their zinc(II) complexes (ZnpXy and ZnmXy) to duplex DNA are described. H₂pXy and H₂mXy bound to calf thymus DNA (CTDNA) stronger than unichromophoric H₂TMPyP, and showed exciton-type induced circular dichroism spectra of their Soret bands. The H₂TMPyP-like units of the metal-free bis-porphyrins did not intercalate into CTDNA, and thus the binding mode is outside binding with intramolecular stacking. ZnpXy showed favorable binding to A·T over G·C region, and should lie in the major groove of A·T region. Full article

Urinary tract infection by Proteus mirabilis depends on several virulence properties that are coordinately regulated with swarming differentiation. Here we report the antibacterial and anti-swarming effect of seventeen terpenoids, and the effect of subinhibitory concentrations of five selected terpenoids on swarming, biofilm formation and haemolysin activity. The results showed that all the terpenes evaluated, particularly oxygenated terpenoids, inhibited P. mirabilis with MIC values ranging between 3 and 10 mg/L. Moreover, citral, citronellol and geraniol effectively inhibit P. mirabilis swarming in a dose dependent manner, reducing swimming/swarming cell differentiation and haemolysin activity at 1/10 MIC concentration. The inhibition of P. mirabilis swarming and virulence factor expression by selected oxygenated terpenoids suggest that essential oils with high concentration of these compounds have the potential to be developed as products for preventing P. mirabilis infections. Full article

Enantioselective syntheses from dimethyl tartrate of 1,3,5-triazine homo-N-nucleoside analogs, containing a 1,4-dioxane moiety replacing the sugar unit in natural nucleosides, were accomplished. The triazine heterocycle in the nucleoside analogs was further substituted with combinations of NH₂, OH and Cl in the 2,4-triazine positions. Full article

Molecular imprinting is one of the most efficient methods for preparing synthetic receptors that possess user defined recognition properties. Despite general success of non-covalent imprinting for a large variety of templates, some groups of compounds remain difficult to tackle due to their structural complexity. In this study we investigate preparation of molecularly imprinted polymers that can bind sulfonamide compounds, which represent important drug candidates. Compared to the biological system that utilizes metal coordinated interaction, the imprinted polymer provided pronounced selectivity when hydrogen bond interaction was employed in an organic solvent. Computer simulation of the interaction between the sulfonamide template and functional monomers pointed out that although methacrylic acid had strong interaction energy with the template, it also possessed high non-specific interaction with the solvent molecules of tetrahydrofuran as well as being prone to self-complexation. On the other hand, 1-vinyl-imidazole was suitable for imprinting sulfonamides as it did not cross-react with the solvent molecules or engage in self-complexation structures. Full article

We have studied changes in the antibacterial activity and the mode of action of farnesol against Staphylococcus aureus when two terpene alcohols with an aliphatic carbon chain were added, individually, to a bacterial suspension that contained farnesol. Geraniol increased the growth-inhibitory activity of farnesol, but suppressed its ability to damage cell membranes, which is one of the predominant features of the growth-inhibitory activity of farnesol. Geranylgeraniol decreased the growth-inhibitory activity of farnesol and also suppressed its cell-damaging activity. It is possible that the presence of a terpene alcohol can both enhance and suppress the antibacterial activity of farnesol, and even change its mode of action. Thus, it is important to study not only the antibacterial activity of each constituent of an essential oil but also the interactions between them in efforts to characterize the antibacterial activity of the essential oil. Full article

In this paper we describe a novel method for detecting many DNA fragments through efficient amplification by using an emulsion system based on “on-chip” PCR instead of conventional multiplex polymerase chain reaction (PCR). During the preparation of on-chip PCR, a set of primers were immobilized on a slide and other sets were in an emulsion system. Different emulsion phase primers and other related PCR components were dispersed in different droplets of the emulsion system, and then, due to the thermal instability of emulsion droplets, they would be released onto the surface of the slide after preheating in the first PCR step. To test the above method, we used plasma DNAs from pregnant women who was carrying a male fetus for gender identification. Four different Y chromosome DNA fragments were selected. Results showed that different DNA fragments could be simultaneously amplified with satisfactory results. It is suggested that a simple, convenient and inexpensive on-chip PCR method has been developed. Full article

Nicotinic acid (also known as vitamin B3) is a dietary element essential for physiological and antihyperlipidemic functions. This study reports the synthesis of novel mixed ligand complexes of copper with nicotinic and other select carboxylic acids (phthalic, salicylic and anthranilic acids). The tested copper complexes exhibited superoxide dismutase (SOD) mimetic activity and antimicrobial activity against Bacillus subtilis ATCC 6633, with a minimum inhibition concentration of 256 μg/mL. Copper complex of nicotinic-phthalic acids (CuNA/Ph) was the most potent with a SOD mimetic activity of IC₅₀ 34.42 μM. The SOD activities were observed to correlate well with the theoretical parameters as calculated using density functional theory (DFT) at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complex CuNA/Ph was positively correlated with the electron affinity (EA) value. The two quantum chemical parameters, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), were shown to be appropriate for understanding the mechanism of the metal complexes as their calculated energies show good correlation with the SOD activity. Moreover, copper complex with the highest SOD activity were shown to possess the lowest HOMO energy. These findings demonstrate a great potential for the development of value-added metallovitamin-based therapeutics. Full article

A new pregnanone, named calotropone (1), was isolated from the EtOH extract of the roots of Calotropis gigantea L. together with a known cardiac glycoside. The structures were elucidated by a study of their physical and spectral data. Compounds 1 and 2 displayed inhibitory effects towards chronic myelogenous leukemia K562 and human gastric cancer SGC-7901 cell lines. Full article

Proanthocyanidins are present in many fruits and plant products like grapes and wine, and contribute to their taste and health benefits. In the past decades of years, substantial progresses has been achieved in the identification of composition and structure of proanthocyanidins, but the debate concerning the existence of an enzymatic or nonenzymatic mechanism for proanthocyanidin condensation still goes on. Substantial attention has been paid to elucidating the potential mechanism of formation by means of biomimetic and chemical synthesis in vitro. The present paper aims at summarizing the research status on chemical synthesis of proanthocyanidins, including non-enzymatic synthesis of proanthocyanidin precursors, chemical synthesis of proanthocyanidins with direct condensation of flavanols and stereoselective synthesis of proanthocyanidins. Proanthocyanidin-involved reactions in aging wines are also reviewed such as direct and indirect reactions among proanthocyanidins, flavanols and anthocyanins. Topics for future research in this field are also put forward in this paper. Full article

As multiple mechanisms account for polyphenol-induced cytotoxicity, the development of structure-activity relationships (SARs) may facilitate research on cancer therapy. We studied SARs of representatives of 10 polyphenol structural types: (+)-catechin (1), (-)-epicatechin (2), (-)-epigallocatechin (3), (-)-epigallocatechin gallate (4), gallic acid (5), procyanidin B2 (6), procyanidin B3 (7), procyanidin B4 (8), procyanidin C1 (9), and procyanidin C2 (10). Amongst them, the polyphenols containing a pyrogallol moiety (3-5) showed the most potent cytotoxicic activity. These compounds evoked a typical DNA-laddering phenomenon in HEK293T, which indicated that the induction of apoptosis at least partly mediates their cytotoxic activity. Anti-oxidative capacity of compounds 3-5 were comparable to those of the trimers 9 and 10, which were not cytotoxic. Therefore, we suggest that pyrogallol moiety is important for fitting of polyphenols to their putative target molecule(s) in non-oxidative mechanism. Full article

Using acid-catalyzed degradation in the presence of cysteamine, the condensed tannins from Lithocarpus glaber leaves were characterized, following thiolysis, by means of reversed-phase HPLC, ¹³C-NMR and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analyses. The thiolysis reaction products showed the presence of the procyanidin (PC) and prodelphinidin (PD) structures. The ¹³C-NMR spectrum revealed that the condensed tannins were comprised of PD (72.4%) and PC (27.6%), and with a greater content of cis configuration rather than the trans configuration of C2–C3. The MALDI-TOF MS analysis proved the presence of PD units, and the maximum degree of polymerization (DP) was an undecamer. The antioxidant activity of condensed tannins from L. glaber leaves was evaluated by using a free radical scavenging activity assay. Full article

Invasion of cancer cell induced by matrix metalloproteinase-9 (MMP-9) is one of pivotal steps in cancer metastasis. Herein, we investigated how cell invasion was regulated by berberine (BBR), an isoquinoline derivative alkaloid compound, in MDA-MB-231 human breast cancer cells. The basal level of MMP-9 activity and expression was dose-dependently increased by TNF-α, while TNF-a-induced MMP-9 gelatinase activity and expression was decreased by BBR. To investigate regulatory mechanism of TNF-α-induced MMP-9 expression, we pretreated cells with UO126 (MEK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor), respectively. Interestingly, TNF-α-induced MMP-9 activity and expression was decreased by UO126 and SB203580, but not by SP600125. Therefore, we further examined the effects of BBR on TNF-α-induced AP-1 DNA binding activity which is a downstream target of ERK and p38. Our data showed that TNF-α-induced AP-1 DNA binding activity was inhibited by BBR. Finally, we investigated the effect of BBR on TNF-α-induced cell invasion. TNF-α-induced cell invasion was significantly decreased by BBR treatment. Taken together, we suggest that TNF-α-induced MMP-9 expression and cell invasion are decreased by BBR through the suppression of AP-1 DNA binding activity in MDA-MB-231 human breast cancer cells. Full article

Dehydroaltenusin is a selective inhibitor of mammalian DNA polymerase α (pol α) from a fungus (Alternaria tennuis). We have designed, synthesized, and characterized a derivative of dehydroaltenusin conjugated with a C12-alkyl side chain (dehydroaltenusin-C12 [C12]). C12 was the strongest pol α inhibitor in vitro. We introduced C12 into NIH3T3 cells with the help of a hypotonic shift, that is, a transient exposure of cultured cells in hypotonic buffer with small molecules which can not penetrate cells. The cells that took in C12 by hypotonic shift showed cell growth inhibition. At a low concentration (5 μM), DNA replication was inhibited and several large replication protein A (RPA) foci, which is different from dUTP foci. Furthermore, when C12 was incubated with aphidicolin, RPA foci were not observed in cells. Finally, these findings suggest that C12 inhibited DNA replication through pol α inhibition, and generated single-stranded DNA, resulted in uncoupling of the leading strand and lagging strand synthesis. These findings suggest that C12 could be more interesting as a molecule probe or anticancer agent than aphidicolin. C12 might provide novel markers for the development of antiproliferative drugs. Full article

The structures previously assigned to (+)-laurelliptinhexadecan-1-one (1a) and (+)-laurelliptinoctadecan-1-one (1b) from Cocculus orbiculatus (L.) DC. (Menispermaceae) have been confirmed by total synthesis of the racemic alkaloids. The key step of the synthesis involved formation of ring C of the aporphines by a radical-intiated cyclisation. Both (±)-laurelliptinhexadecan-1-one (1a) and (±)-laurelliptinoctadecan-1-one (1b) were inactive against Staphylococcus aureus ATCC25932, Escherichia coli ATCC10536 and Candida albicans ATCC90028. Full article

Allium leucanthum C. Koch is an endemic Caucasian species that grows in Georgia. The flowers are used in traditional medicine. Phytochemical investigation allowed the isolation of seven spirostanol type saponins from the flowers. Their structures were elucidated on the base of NMR and HRESIMS spectrometry data. A new compound, which we have named leucospiroside A (5), has been identified as (25R)-5α-spirostane-2α,3β,6β-triol 3-O-β-glucopyranosyl-(1→3)-β-glucopyranosyl-(1→2)-[β-glucopyranosyl-(1→3)]-β-glucopyranosyl-(1→4)-β-galactopyranoside. The six others were known substances, but are described in this plant for the first time. The crude extract, spirostanol and furostanol fractions, as well as isolated compounds, were evaluated for their in vitro cytotoxic activity. Compounds 1-3 and 5 were found to be the most active, with relatively similar IC50 values ranging from 3.7 to 5.8 μM for a lung cancer cell line (A549) and 5.6 to 8.2 μM for a colon cancer cell line (DLD-1). Full article