Novel 2′-substituted flavonols from the farinose exudate of Notholaena affinis

The farinose exudate produced on the undersurface of fronds of Notholaena affinis consists of a variety of lipophilic flavonol aglycones. Four of these have been identified as novel interrelated compounds. They all bear methoxyl groups in positions 3,6,7,8 and hydroxyl and/or methoxyl groups at 2′,4′.     

Structure–activity relationships of diverse xanthones against multidrug resistant human tumor cells

Thirteen xanthones were isolated naturally from the stem of Securidaca inappendiculata Hassk, and structure-activity relationships (SARs) of these compounds were comparatively predicted for their cytotoxic activity against three human multidrug resistant (MDR) cell lines MCF-7/ADR, SMMC-7721/Taxol, and A549/Taxol cells. The results showed that the selected xanthones exhibited different potent cytotoxic activity against the growth of different human tumor cell lines, and most of the xanthones exhibited selective cytotoxicity against SMMC-7721/Taxol cells. Furthermore, some tested xanthones showed stronger cytotoxicity than Cisplatin, which has been used in clinical application extensively. The SARs analysis revealed that the cytotoxic activities of diverse xanthones were affected mostly by the number and position of methoxyl and hydroxyl groups. Xanthones with more free hydroxyl and methoxyl groups increased the cytotoxic activity significantly, especially for those with the presence of C-3 hydroxyl and C-4 methoxyl groups.     

Oxygen fixation in the biosynthesis of ferulic acid by green Zea mays

The results of experiments in which seedlings of Zea mays were grown in the light in an atmosphere enriched with oxygen-18 indicate that the hydroxyl and methoxyl oxygen atoms in ferulic acid are derived from molecular oxygen.     

Investigation of Lignin-water interactions by molecular simulation

The results of molecular dynamics simulations of three lignin-water systems are presented. Static and dynamic properties of each system are compared to a benchmark system consisting entirely of water molecules. The significantly reduced mobility of water molecules local to lignin hydroxyl regions is attributed to hydrogen bond formation, while the slightly reduced mobility of water molecules in the vicinity of lignin methoxyl groups results from a hydrophobic effect that causes water molecules to structure themselves around these groups. The average diffusion of water in each system correlates with the number of methoxyl groups present in the system. As the number of methoxyls in the system increases, so too does the average diffusion constant of water in that system. The bulky methoxyl groups obstruct water from accessing lignin hydroxyl regions where hydrogen bond formation is anticipated and the hydrogen-bonded water lowers the average diffusion constant.     

Effects of solute methoxylation on glass-forming ability and stability of vitrification solutions

The effects of replacing hydroxyl groups with methoxyl (OCH(3)) groups in the polyols ethylene glycol (EG), propylene glycol (PG), glycerol, and threitol were studied by differential scanning calorimetry (DSC) during cooling of aqueous solutions to -150 degrees C and subsequent rewarming. For 35% (w/w) PG, 40% EG, and 45% glycerol, a single substitution of a terminal hydroxyl group with a methoxyl group reduced the critical cooling rate necessary to avoid ice on cooling (vitrify) from approximately 500 to 50 degrees C/min. This reduction was approximately equivalent to increasing the parent polyol concentration by 5% (w/w). The critical warming rate calculated to avoid formation of ice on rewarming (devitrification) was also reduced by methoxyl substitution, typically by a factor of 10(4) for dilute solutions. Double methoxylation (replacement of both terminal hydroxyls) tended to result in hydrate formation, making these compounds less interesting. An exception was threitol, for which substituting both terminal hydroxyls by methoxyls reduced the critical rewarming rate of a 50% solution by a factor of 10(7) without any hydrate formation. These glass-forming and stability properties of methoxylated compounds, combined with their low viscosity, enhanced permeability, and high glass transition temperatures, make them interesting candidate cryoprotective agents for cryopreservation by vitrification or freezing. Copyright 1999 Academic Press.     

Isolation and Structural Identification of a New Metabolite of Fusarium equiseti

A fluorescent compound was isolated and purified from rice cultures of Fusarium equiseti (Alaska 2-2). Mass spectrometry and nuclear magnetic resonance data indicated that its structure is 2,2-dimethyl-5-amino-6-(3′-hydroxyl-4′-methoxyl-butyryl)-4-chromone. It is an analog of the mycotoxin fusarochromanone, in which the amino group on C-3′ is replaced by a hydroxyl group and the hydroxyl group on C-4′ is replaced by a methoxyl group.     

Molecular structural effects involved in the interaction of anthracyclines with DNA.

Changes in DNA binding ability of daunomycin following structural modifications in the aglycone moiety have been studied by the fluorescence quenching method and by thermal denaturation of the complex. Removal of the methoxyl group at position 4 leads to a slightly stronger binding. Changes in the position of the glycosidic linkage result in a markedly weaker binding. Removal of the hydroxyl group at position 9, with the concomitant formation of a 9,10-anhydro derivative, decreases the binding ability. Methylation of hydroxyl groups at C-6 and C-11 leads to an inactive derivative and makes the binding affinity disappear almost completely. Structure-activity correlations for the DNA binding reaction deduced from these studies are in agreement with earlier findings that relate to the biological activity and confirm the general picture of the binding mechanism.     

Structure-activity relationship of flavonoids with superoxide scavenging activity

The superoxide scavenging activities of 12 flavonoids were measured. The superoxide anions were generated by a hypoxanthine-xanthine oxidase system and measured by the nitrite method. The results showed that the scavenging ability enhanced with an increasing number of hydroxyl groups in rings B. Substitution at C3 position with a hydroxyl group increased the activity. Compared to a methoxyl group or a glycoside in this position, a free hydroxyl group showed the highest activity. A saturated C2−C3 bond showed a higher activity than a unsaturated bond. The absence of a carbonyl group at C4 position increased the activity.     

Antibacterial activities of viriditoxin congeners and synthetic analogues against fish pathogens

Viriditoxin is a fungal secondary metabolite of the fungus Paecilomyces variotii derived from the inner tissues of the giant jellyfish Nemopilema nomurai. Viriditoxin exhibits antibacterial activity against Streptococcus iniae and Streptococcus parauberis, which are major pathogens of aqua cultured fish. Viriditoxin induced abnormal cell morphologies in the fish pathogens S. iniae and S. parauberis, presumably by inhibiting FtsZ polymerization as was previously observed in Escherichia coli. Synthetic analogues of viriditoxin, designed based on docking simulation results to FtsZ of Staphylococcus aureus, were prepared and compared with viriditoxin for antibacterial activity. Reconstitution of free hydroxyl or carboxyl groups of the methoxyl or methyl ester groups of viriditoxin led to significant reduction of antibacterial activity, implying that the natural molecule is optimized for antibacterial activity to deter bacteria potentially harmful to Paecilomyces.     

Partial characterization of a phenolic pigment from sporocarps of Phellinus igniarius

A dark brown phenolic polymer, isolated from mature sporocarps of Phellinus igniarius (DC. ex Fr.) Quél., is responsible for the darkening of sporocarp tissue when a drop of base is applied. The pigment is rich in aliphatic as well as phenolic hydroxyl groups, and also contains significant numbers of carboxyls and carbonyls. The presence of 3,4-dihydroxyphenyl moieties was documented by the identification of veratric and metahemipinic acids from oxidative degradation of methylated samples. Despite a 2% methoxyl content, the polymer contains no guaiacyl or syringyl moieties and therefore contains no lignin. It appears to be formed by the oxidative polymerization of a molecule containing a 3,4-dihydroxystyryl moiety. Hispidin was identified as its trimethyl ether in methylated extracts of pigmented mycelial mats of Phellinus igniarius grown in liquid culture.     

P.m.r. studies on fully methylated disaccharides using lanthanide shift reagents: assignments of the methoxyl signals

The complexes of Eu(fod)₃ with per-O-methylated aldohexosylaldohexoses, consisting of d-glucopyranose and d-galactopyranose residues and having (1→2), (1→4), and (1→6) linkages, have been studied by using p.m.r. spectroscopy. It was found that Eu(fod)₃ binds preferentially to two neighbouring MeO-oxygens having an axial-equatorial relationship. Steric hindrance is a major factor in disfavouring certain sites. On the basis of Eu(fod)₃-effects on the methoxyl groups, and the comparison of the chemical shifts of corresponding groups in the permethylated mono- and di-saccharides, the signals for most of the Meo groups of the latter compounds were assigned. The shift increments of the signals for these MeO groups, with respect to those for the corresponding groups in the permethylated monomers, were related to the type and the configuration of the inter-sugar linkage. The potential of the shift increments for assignment purposes in other permethylated di- or higher-saccharides is discussed.     

A chemical analog of curcumin as an improved inhibitor of amyloid Abeta oligomerization

Amyloid-like plaques are characteristic lesions defining the neuropathology of Alzheimer's disease (AD). The size and density of these plaques are closely associated with cognitive decline. To combat this disease, the few therapies that are available rely on drugs that increase neurotransmission; however, this approach has had limited success as it has simply slowed an imminent decline and failed to target the root cause of AD. Amyloid-like deposits result from aggregation of the Aβ peptide, and thus, reducing amyloid burden by preventing Aβ aggregation represents an attractive approach to improve the therapeutic arsenal for AD. Recent studies have shown that the natural product curcumin is capable of crossing the blood-brain barrier in the CNS in sufficient quantities so as to reduce amyloid plaque burden. Based upon this bioactivity, we hypothesized that curcumin presents molecular features that make it an excellent lead compound for the development of more effective inhibitors of Aβ aggregation. To explore this hypothesis, we screened a library of curcumin analogs and identified structural features that contribute to the anti-oligomerization activity of curcumin and its analogs. First, at least one enone group in the spacer between aryl rings is necessary for measureable anti-Aβ aggregation activity. Second, an unsaturated carbon spacer between aryl rings is essential for inhibitory activity, as none of the saturated carbon spacers showed any margin of improvement over that of native curcumin. Third, methoxyl and hydroxyl substitutions in the meta- and para-positions on the aryl rings appear necessary for some measure of improved inhibitory activity. The best lead inhibitors have either their meta- and para-substituted methoxyl and hydroxyl groups reversed from that of curcumin or methoxyl or hydroxyl groups placed in both positions. The simple substitution of the para-hydroxy group on curcumin with a methoxy substitution improved inhibitor function by 6-7-fold over that measured for curcumin.     

Steroidal saponins from Asparagus africanus.

The structures of two new monodesmosidic spirostanosides and a new bisdesmosidic furostanol glycoside isolated from the roots of Asparagus africanus Lam. (Liliaceae) have been elucidated as (25R)-3 beta-hydroxy-5 beta-spirostan-12-one 3-O-{beta-D-glucopyranosyl-(1-->2)-[alpha-1-arabinopyranosyl-(1--> 6)]-beta- D-glucopyranoside} (1), (25R)-5 beta-spirostan-3 beta-ol 3-O-{beta-D-glucopyranosyl-(1-->2)-[alpha-L-arabinopyranosyl-(1--> 6)]-beta- D-glucopyranoside} (2) and 26-O-beta-D-glucopyranosyl]-22 alpha-methoxy-(25R)-furostan-3 beta,26-diol 3-O-{beta-D-glucopyranosyl-(1-->2)-[beta-D-glucopyranoside} (3), respectively, by the combined use of one and two dimensional NMR experiments. The complete 13C and 1H assignments of the peracetyl spirostanosides and the furostanol oligoside were derived. The interconversions between the methoxyl and hydroxyl group at C-22 of the furostanol glycoside was investigated and the genuine furostanol oligoside of A. africanus appears to be the hydroxyl type based on the comparative study of the methanol, pyridine and dioxane extracts.     

NMR study of the complexation of D-gulonic acid with tungsten(VI) and molybdenum(VI)

By using multinuclear (1H, 13C, 17O, 95Mo, 183W) magnetic resonance spectroscopy (1D and 2D), D-gulonic acid is found to form ten and seven complexes, respectively, with tungsten(VI) and molybdenum(VI), in aqueous solution, depending on pH and metal-ligand molar ratios. Two isomeric 1:2 (metal-ligand) complexes involving the carboxylate and the adjacent OH group are present in the pH range 2-9. At intermediate and high pH, molybdate forms a 2:1 tetradentate complex involving the four secondary hydroxyl groups, whereas tungstate forms one 2:1 terdentate species. At low and intermediate pH values, three 2:1 complexes are found for both metals, involving the carboxylate group and three secondary hydroxyl groups, as well as a 5:2 species involving the carboxylate group and all the secondary hydroxyl groups; the concentration of this species increases in time mainly at the expense of 2:1 and 1:2 complexes. Tungstate can also form two additional species, probably a 5:2 species involving the carboxylate group and all the hydroxyl groups, and a 2:1 pentadentate species involving the carboxylate group and all the secondary hydroxyl groups. In alkaline solutions, tungstate is able to form an additional 2:1 pentadentate complex involving all the hydroxyl groups.     

In vitro analysis of iron chelating activity of flavonoids

Flavonoids have been demonstrated to possess miscellaneous health benefits which are, at least partly, associated with iron chelation. In this in vitro study, 26 flavonoids from different subclasses were analyzed for their iron chelating activity and stability of the formed complexes in four patho/physiologically relevant pH conditions (4.5, 5.5, 6.8, and 7.5) and compared with clinically used iron chelator deferoxamine. The study demonstrated that the most effective iron binding site of flavonoids represents 6,7-dihydroxy structure. This site is incorporated in baicalein structure which formed, similarly to deferoxamine, the complexes with iron in the stoichiometry 1:1 and was not inferior in all tested pH to deferoxamine. The 3-hydroxy-4-keto conformation together with 2,3-double bond and the catecholic B ring were associated with a substantial iron chelation although the latter did not play an essential role at more acidic conditions. In agreement, quercetin and myricetin possessing all three structural requirements were similarly active to baicalein or deferoxamine at the neutral conditions, but were clearly less active in lower pH. The 5-hydroxy-4-keto site was less efficient and the complexes of iron in this site were not stable at the acidic conditions. Isolated keto, hydroxyl, methoxyl groups or an ortho methoxy-hydroxy groups were not associated with iron chelation at all.     

The system of xylogalactans from the red seaweed Jania rubens (Corallinales, Rhodophyta)

The main acidic polysaccharides from the red seaweed Jania rubens share the general characteristics of corallinans (agar-like xylogalactans). After fractionation by ion-exchange chromatography, ten fractions were separated and characterized by sugar composition, other components, methylation, ethylation, desulfation-methylation, and NMR analyses. The main group of fractions carry the agaran disaccharidic repeating unit [-->3)-beta-d-Gal-(1-->4)-alpha-l-Gal-(1-->] substituted mainly on O-6 of the beta-d-Gal unit by beta-xylosyl side stubs, and less with sulfate or methoxyl groups, and also on O-2 of the alpha-l-Gal unit with methoxyl or sulfate, or less on O-3 of the same unit with methoxyl groups. These features are somehow common to the four members of the order already studied. However, a sugar uncommon to the order appears in moderate proportions for all the fractions: it is 3,6-anhydro-l-galactose (partly sulfated or methoxylated on O-2) replacing the l-Gal unit. Besides, several other structural features never found in the order (and uncommon in any polysaccharide) appear in some minor fractions: the presence of side stubs of 2,3-di- and 3-O-methyl-d-galactose, and also part of the 3-O-methyl-l-galactose acting as side stubs. These results show that, although the main features of the corallinean xylogalactans are common to all the species studied, each one has minor characteristics of its own.     

Production of a novel bioflocculant by Bacilluslicheniformis X14 and its application to low temperature drinking water treatment

A novel bioflocculant ZS-7 produced by Bacillus licheniformis X14 was investigated with regard to its synthesis and application to low temperature drinking water treatment. The effects of culture conditions including pH, carbon source, nitrogen source, temperature, inoculum size and shaking speed on ZS-7 production were studied. The purified bioflocculant was identified as a glycoprotein consisting of polysaccharide (91.5%, w/w) and protein (8.4%, w/w), with an approximate molecular weight of 6.89 × 10⁴ Da. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) indicated the presence of amino, amide, carboxyl, methoxyl and hydroxyl groups. This bioflocculant showed good flocculating performance and industrial potential for treatment of low temperature drinking water, and the maximum removal efficiencies of COD_Mn and turbidity were 61.2% and 95.6%, respectively, which were better than conventional chemical flocculants. Charge neutralization and bridging were proposed as the reasons for the enhanced performance based upon the experimental observations.     

Palladium(II) complexes bearing a salicylaldiminato ligand with a hydroxyl group: Synthesis, structures, deprotonation, and catalysis

Palladium complexes with a salicylaldiminato ligand bearing a hydroxyl group (1a and 1b) have been synthesized and characterized. The structures of these complexes were confirmed by X-ray crystallography. A reversible deprotonation/protonation of the hydroxyl moiety on 1b was observed, while such behaviour was impossible with a related palladium complex (1c) bearing a methoxyl group in place of the hydroxyl group. The deprotonation affected its catalytic behaviour: the activity for polymerization of methyl acrylate catalyzed by 1b considerably decreased in the presence of 1 equiv. of ^tBuOK.     

C-Aryl glycoside inhibitors of SGLT2: Exploration of sugar modifications including C-5 spirocyclization

Modifications to the sugar portion of C-aryl glycoside sodium glucose transporter 2 (SGLT2) inhibitors were explored, including systematic deletion and modification of each of the glycoside hydroxyl groups. Based on results showing activity to be quite tolerant of structural change at the C-5 position, a series of novel C-5 spiro analogues was prepared. Some of these analogues exhibit low nanomolar potency versus SGLT2 and promote urinary glucose excretion (UGE) in rats. However, due to sub-optimal pharmacokinetic parameters (in particular half-life), predicted human doses did not meet criteria for further advancement.     

Importance of the B ring and its substitution on the alpha-glucosidase inhibitory activity of baicalein, 5,6,7-trihydroxyflavone

Hydroxychromones and B-ring-substituted 5,6,7-trihydroxyflavones were prepared to evaluate the contribution of the B ring of baicalein (5,6,7-trihydroxyflavone, 1) to its potent alpha-glucosidase inhibitory activity. Hydroxychromones, which lack 6-hydroxyl substitution, did not show any inhibitory activity, while 5,6,7-trihydroxy-2-methylchromone (5) showed high activity. Among the tested B-ring-substituted 5,6,7-trihydroxyflavones, the 4'-hydroxy-, 3',4'-dihydroxy-, and 3',4',5'-trihydroxy-substituted derivatives were found to give more activity than that of 1. The methoxy-substituted derivatives, however, showed less activity than 1. The results suggest that the B ring of 1 was not essential, although advantageous to the activity; hydroxyl substitution on the B ring of 5,6,7-trihydroxyflavones was favorable to the activity, whereas methoxyl substitution was unfavorable; at least 4'-hydroxyl substitution of 5,6,7-trihydroxyflavones was required for enhanced activity, in which the number of hydroxyl groups did not take part.