Regioselective pyrrolizidine bis-spirooxindoles as efficient anti-amyloidogenic agents.

Here, we report a microwave-assisted, one-pot, three-component, 1,3-dipolar cycloaddition reaction to produce highly regioselective and stereoselective bis-spirooxindoles as potential inhibitors against amyloid-β fibrillation. Ease of synthesis, promising anti-amyloidogenic activity, low toxicity, and in vitro blood brain barrier permeability makes these compounds attractive therapeutic leads to treat Alzheimer's disease.

Microwave-assisted rapid synthesis of spirooxindole-pyrrolizidine analogues and their activity as anti-amyloidogenic agents.

A library of Sox-pyrrolizidines was rapidly prepared by microwave-assisted, one-pot, three-component, 1,3-dipolar cycloaddition of azomethine ylides from l-proline and isatin, with various β-nitrostyrenes. Nitro-Sox compounds, 4b, 4d and 4e inhibit HEWL amyloid fibril formation by ThT studies with percentages of fluorescence intensity of 55.4, 42.

Natural spirocyclic alkaloids and polyphenols as multi target dementia leads.

The U rhynchophylla, U tomentosa, Isatis indigotica Fortune, Voacanga Africana, herbal constituents, fungal extracts from Aspergillus duricaulis culture media, include spirooxindoles, polyphenols or bridged spirocyclic alkaloids. Their constituents exhibit specific and synergistic multiple neuroprotective properties including inhibiting of Aβ fibril induced cytotoxicity, NMDA receptor inhibition in mice models of Alzheimer's disease (AD). The pioneering research from Woodward to Waldmann has advanced the synthesis of spirocyclic alkaloids.

Macrolactam analogues of macrolide natural products.

The chemical modification of macrolide natural products into aza- or lactam analogues is a strategy employed to improve their metabolic stability and biological activity. The methods for the synthesis of several lactam analogues of macrolide natural products are highlighted and aspects of their biological properties presented.

Polyphenol protection and treatment of hypertension.

Introduction: High blood pressure is the major risk factor for cardiovascular diseases and the rising prevalence of human hypertension precedes the trend toward a global epidemic of unhealthy ageing. A focus on lifestyle and dietary interventions minimizes dependency on pharmacological antihypertensive therapies.

Review: Observational studies indicate that the intake of dietary flavonoids is associated with a decreased risk of cardiovascular disease (CVD).

Synthesis and biological evaluation of 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one structural derivatives as anti-cancer and apoptosis inducing agents.

A series of thirteen 5H-dibenzo [b,e][1,4]diazepin-11(10H)-one structural derivatives has been synthesized and evaluated for anti-proliferative activity against five human cancer cell lines. Compound 9a exhibited potent tumour growth inhibition in all cell lines with IC50 values in the range of 0.71-7.

Fenugreek increases insulin-stimulated creatine content in L6C11 muscle myotubes.

Purpose: Creatine uptake by muscle cells is increased in the presence of insulin. Accordingly, compounds with insulin-like actions may also augment creatine uptake. The aim of this study was to investigate whether Trigonella foenum-graecum (fenugreek), an insulin mimetic, increases total intracellular creatine levels in vitro.

Brain Food for Alzheimer-Free Ageing: Focus on Herbal Medicines.

Healthy brain aging and the problems of dementia and Alzheimer's disease (AD) are a global concern. Beyond 60 years of age, most, if not everyone, will experience a decline in cognitive skills, memory capacity and changes in brain structure. Longevity eventually leads to an accumulation of amyloid plaques and/or tau tangles, including some vascular dementia damage.

Anti-amyloidogenic properties of some phenolic compounds.

A family of 21 polyphenolic compounds consisting of those found naturally in danshen and their analogues were synthesized and subsequently screened for their anti-amyloidogenic activity against the amyloid beta peptide (Aβ42) of Alzheimer's disease. After 24 h incubation with Aβ42, five compounds reduced thioflavin T (ThT) fluorescence, indicative of their anti-amyloidogenic propensity (p < 0.001).

Danshen diversity defeating dementia.

Salvia miltiorrhiza (danshen) is widely used for the clinical treatment of cerebral ischemia and cardiovascular diseases. Its diverse molecular makeup of simple and poly hydroxycinnamic acids and diterpenoid quinones are also associated with its beneficial health effects such as improved cognitive deficits in mice, protection of neuronal cells, prevention of amyloid fibril formation and preformed amyloid fibril disaggregation related to Alzheimer's disease. Whilst the in vitro studies have therapeutic promise, the anti-dementia effect/impact of danshen however depends on its absorbed constituents and pharmacokinetic properties.

Bridging the gap: basic metabolomics methods for natural product chemistry.

Natural products and their derivatives often have potent physiological activities and therefore play important roles as both frontline treatments for many diseases and as the inspiration for chemically synthesized therapeutics. However, the detection and synthesis of new therapeutic compounds derived from, or inspired by natural compounds has declined in recent years due to the increased difficulty of identifying and isolating novel active compounds. A new strategy is therefore necessary to jumpstart this field of research.

Natural product chemistry in action: the synthesis of melatonin metabolites K₁ and K₂.

Natural product chemistry often yields new compounds with great potential for economic and/or health benefits. However, most natural compounds must be artificially synthesized on an industrial scale to generate enough active ingredients to be commercially viable. Thus chemical synthesis is an essential tool of natural product chemistry.

Tandem nucleophilic addition-Oppenauer oxidation of aromatic aldehydes to aryl ketones with triorganoaluminium reagents.

In the presence of pinacolone, the in situ prepared triorganoaluminium reagents reacted with aromatic aldehydes to give ketones in moderate to high yield. We propose that the products are formed via a tandem organoaluminium reagents addition-Oppenauer oxidation sequence.

A modeling approach for orthogonality of comprehensive two-dimensional separations.

A novel method is developed for orthogonality evaluation of comprehensive two-dimensional separations (C2DS). Utilization of efficiency measures such as peak capacity (n(c)) can be critically evaluated for C2DS analysis to describe an orthogonal separation of the analytes in a 2D plane. Unlike most previous methods focusing on "bin coverage" over 2D space, rather than taking into account the distribution based on accurate peak retention, in the proposed method, the separation orthogonality of C2DS is divided into two parts (i.

Simultaneous estimation of retention times of overlapping primary peaks in comprehensive two-dimensional GC.

A general approach is developed to estimate the retention time (t(R)) of overlapping primary peaks in comprehensive 2D GC without assumptions such as the limitation of modulation ratio or symmetry of the target primary peak. Accurate determination of t(R) can recover the original peak profile by using mathematical fitting. First, the modulation pattern of the first-dimension peak in the second dimension is summarized with the number of major modulation fractions equal to or less than four.

Total synthesis of (+)-pentamethylsalvianolic acid C.

The total synthesis of a methylated analogue of (+)-Salvianolic acid C has been achieved. Key aspects of the synthetic route include an economical Cu(I) acetylide coupling, unique carboxyl activation conditions via microwave irradiation and a novel lipase catalysed kinetic resolution of a racemic mixture of secondary alcohol Danshensu. The preparation of this methylated analogue will not only improve the bioavailability, but also enable access to new and wider bioactivity applications for (+)-Salvianolic acid C.

Trimethylsilyl chloride promoted synthesis of α-branched amines by nucleophilic addition of organozinc halides to nitrones.

A general procedure for the nucleophilic addition of organozinc halides with nitrones in the presence of trimethylsilyl chloride has been developed. Trimethylsilyl chloride was found to be both an indispensable reaction promoter and a ready hydroxylamine protective agent in these reactions. The produced O-(trimethylsilyl)hydroxylamines can be easily reduced into corresponding amines just by a zinc-copper couple in saturated aqueous NH(4)Cl solution.

Component correlation between related samples by using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry with chemometric tools.

A chemometric strategy has been developed to discover component difference and similarity between two chromatograms (correlation) by using comprehensive two-dimensional (2D) gas chromatography with time-of-flight mass spectrometry (GC×GC-TOFMS). It allows for rapid determination of the presence or absence of analytes of interest in both pure and overlapping peak clusters, and then locates elution windows of target components. First, representative elution windows of analytes are extracted from the 2D GC×GC map to characterize the spectral space and further construct an orthogonal projection matrix for analysis.

Evaluating the traditional Chinese literature for herbal formulae and individual herbs used for age-related dementia and memory impairment.

Natural products are the basis of many systems of traditional medicine and continue to provide sources for new drugs. Ethnobiological approaches to drug discovery that have proven productive in the past include the investigation of traditional medical literatures. This study describes a broadly applicable method for locating, selecting and evaluating citations in the traditional Chinese herbal medicine literature of the dynastic period (until 1911) for specific symptoms or disorders.

Chemometrics in comprehensive multidimensional separations.

Chemometric methods have critical importance for the discovery of the information/knowledge buried or concealed in high-dimensional datasets acquired from comprehensive multidimensional separations (CMDS), and for interpretation of experiments or chemical processes. In this work, employment of new developments in chemometrics making full use of the data to maximize the potential of CMDS to resolve mathematically a variety of practical problems is reviewed whilst providing the authors' point of view. During the past several years, chemometrics has been successfully applied to many areas of concern to CMDS investigation, including experimental parameter optimization, data quality improvement, identification and quantification of target chemical components, pattern recognition technique for clustering and classification, multivariate model establishment to correlate chromatographic properties and molecular descriptors.

Simultaneous deconvolution and re-construction of primary and secondary overlapping peak clusters in comprehensive two-dimensional gas chromatography.

In this study, simultaneous deconvolution and reconstruction of peak profiles in the first ((1)D) and second dimension ((2)D) of comprehensive two-dimensional (2D) gas chromatography (GC×GC) is achieved on the basis of the property of this new type of instrumental data. First, selective information, where only one component contributes to the peak elution window of a given modulation event, is employed for stepwise stripping of each (2)D peak with the help of pure components corresponding to that compound from the neighbouring modulations. Simulation based on an exponentially modified Gaussian (EMG) model aids this process, where the EMG represents the envelope of all (2)D peaks for that compound.

Microwave multicomponent synthesis.

In the manner that very important research is often performed by multidisciplinary research teams, the applications of multicomponent reactions involving the combination of multiple starting materials with different functional groups leading to the higher efficiency and environmentally friendly construction of multifunctional/complex target molecules is growing in importance. This review will explore the advances and advantages in microwave multicomponent synthesis (MMS) that have been achieved over the last five years.

Marine fragrance chemistry.

The main marine message in perfumery is projected by Calone 1951 (7-methyl-2H-1,5-benzodioxepin-3(4H)-one). Kraft (Givaudan) and Gaudin (Firmenich) further maximized the marine fragrance molecular membership by extending the carbon chain of the 7-Me group. Our research targeted the polar group of the benzodioxepinone parent compound to investigate how this region of molecular makeup resonates with the dominant marine fragrance of the Calone 1951 structure.

Does acupuncture or Chinese herbal medicine have a role in the treatment of allergic rhinitis?

Purpose Of Review: Complementary medicines, including acupuncture and Chinese herbal medicine, are being used increasingly for the management of allergies such as allergic rhinitis. Until relatively recently, however, evidence for the efficacy and safety of these therapies in allergic conditions has been lacking.

Recent Findings: A limited number of well conducted studies, all with small sample sizes, have demonstrated the promising therapeutic potential of acupuncture and Chinese herbal medicine for allergic rhinitis.