Naringenin-Functionalized Gold Nanoparticles and Their Role in α-Synuclein Stabilization.

Misfolding and self-assembly of several intrinsically disordered proteins into ordered ß-sheet-rich amyloid aggregates emerged as hallmarks of several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Here we show how the naringenin-embedded nanostructure effectively retards aggregation and fibril formation of α-synuclein, which is strongly associated with the pathology of Parkinson's-like diseases. Naringenin is a polyphenolic compound from a plant source, and in our current investigation, we reported the one-pot synthesis of naringenin-coated spherical and monophasic gold nanoparticles (NAR-AuNPs) under optimized conditions. The average hydrodynamic diameter of the produced nanoparticle was ∼24 nm and showed a distinct absorption band at 533 nm. The zeta potential of the nanocomposite was ∼-22 mV and indicated the presence of naringenin on the surface of nanoparticles. Core-level XPS spectrum analysis showed prominent peaks at 84.02 and 87.68 eV, suggesting the zero oxidation state of metal in the nanostructure. Additionally, the peaks at 86.14 and 89.76 eV were due to the Au-O bond, induced by the hydroxyl groups of the naringenin molecule. The FT-IR analysis further confirmed strong interactions of the molecule with the gold nanosurface via the phenolic oxygen group. The composite surface was found to interact with monomeric α-synuclein and caused a red shift in the nanoparticle absorption band by ∼5 nm. The binding affinity of the composite nanostructure toward α-synuclein was in the micromolar range (Ka∼ 5.02 × 106 M-1) and may produce a protein corona over the gold nanosurface. A circular dichroism study showed that the nanocomposite can arrest the conformational fluctuation of the protein and hindered its transformation into a compact cross-ß-sheet conformation, a prerequisite for amyloid fibril formation. Furthermore, it was found that naringenin and its nanocomplex did not perturb the viability of neuronal cells. It thus appeared that engineering of the nanosurface with naringenin could be an alternative strategy in developing treatment approaches for Parkinson's and other diseases linked to protein conformation.

Correction to "Porphyrin-Gold Nanomaterial for Efficient Drug Delivery to Cancerous Cells".

[This corrects the article DOI: 10.1021/acsomega.8b00419.].

Pyridine-pyrazole based Al(iii) 'turn on' sensor for MCF7 cancer cell imaging and detection of picric acid.

We report herein the development of a new pyridine-pyrazole based bis-bidentate asymmetric chemosensor that shows excellent turn-on chelation-enhanced Al3+-responsive fluorescence. The presence of two 'hard' phenolic hydroxyl groups plays a pivotal role in switching-on the sensing through coordination to the 'hard' Al3+ ion, while the mechanism can be interpreted by the chelation-enhanced fluorescence (CHEF) process. The X-ray single structure show a planar conjugated structure of the ligand, which was further stabilized by extensive H-bonding and π-π stacking. The photophysical studies related to the sensing behavior of the titular ligand toward aluminum was investigated in detail using various spectroscopic techniques like UV-Vis, photoluminescence, fluorescence and time-correlated single-photon count (TCSPC) and time-resolved NMR. The spectroscopic methods also confirm the selective detection of Al3+ ion in the presence of other metal ions. The theoretical calculations using Density Functional Theory (DFT) and the Time Dependent Density Functional Theory (TD-DFT) provide further insight on the mechanistic aspects of the turn-on sensing behavior including the electronic spectra of both the ligand and the complex. Interestingly, the as-synthesized H2DPC-Al complex can also be utilized as a fluorescence-based sensor for various nitroaromatics including picric acid, for which an INHIBIT logic gate can also be constructed. The as synthesized complex was subsequently used as a fluorescent probe for imaging of human breast adenocarcinoma (MCF7) cells using live cell confocal microscopic techniques.

Conjugation reaction with ferulic acid boosts the antioxidant property of arabinogalactan-protein and enhances its ability to form complex with ß-lactoglobulin.

Ferulic acid was chemically grafted onto the arabinogalactan protein of Aegle marmelos fruit gum using 1,1'-carbonyldiimidazole as coupling reagent. Thus, grafted polysaccharides with different degrees of substitution were prepared and then characterized by gas chromatography/mass spectrometry, size exclusion chromatography, and ultraviolet-visible, infra-red, and nuclear magnetic resonance spectroscopic investigations. Fluorescence spectroscopic investigation showed hydrophobic microdomain formation in grafted polymers. The antioxidant activities of the derivatives, as determined by the 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl radical assay, were strong and increases with increasing the degree of feruloylation. Compared to parental arabinogalactan protein (K = 2.38 × 106 M-1), these grafted polymers bind more strongly with ß-lactoglobulin (K = 11.4 × 106 M-1 and 8.19 × 106 M-1). Given that gum polysaccharides are valuable component in functional foods, synthesis of antioxidative graft polymer possessing good compatibility with ß-lactoglobulin may have important implication.

The heteropolysaccharide of Mangifera indica fruit: Isolation, chemical profile, complexation with ß-lactoglobulin and antioxidant activity.

A 91 kDa heteropolysaccharide (F2) was isolated from Mangifera indica fruit via extraction with H2O, purification by C2H5OH, starch removal and ion exchange chromatography. This polymer was made up mostly of Ara, Gal, Glc, Rha, Xyl, and GalA in a 37: 29: 9:3:2:19 molar proportion. It inherited a small backbone containing GalpA and Rhap units substituted with very large side chains containing differently linked Ara and Gal units plus esterified gallic acid (GA) residue. Several enzymes generated oligosaccharides including (i) Ara2-10Ac6-22, (ii) Gal1-8Ac5-26 and (iii) GA1Gal1Ac7 were characterized. This polysaccharide, which showed dose dependent antioxidant activity, exhibited synergism with gallic acid, and formed a complex (K = 1.2 × 106 M-1) with ß-lactoglobulin. Accordingly, H2O treatment produces a polysaccharide with desired biochemical properties; this could be effective in designing innovative functional food with flexible makeup.

Solvent-Assisted Tyrosine-Based Dipeptide Forms Low-Molecular Weight Gel: Preparation and Its Potential Use in Dye Removal and Oil Spillage Separation from Water.

Low-molecular weight gelators (supramolecular, or simply molecular gels) are highly important molecular frameworks because of their potential application in drug delivery, catalysis, pollutant removal, sensing materials, and so forth. Herein, a small dipeptide composed of N-(tert-butoxycarbonyl)pentafluoro-l-phenylalanine and O-benzyl-l-tyrosine methyl ester was synthesized, and its gelation ability was investigated in different solvent systems. It was found that the dipeptide was unable to form gel with a single solvent, but a mixture of solvent systems was found to be suitable for the gelation of this dipeptide. Interestingly, water was found to be essential for gelation with the polar protic solvent, and long-chain hydrocarbon units such as, petroleum ether, kerosene, and diesel, were important for gelation with aromatic solvents. The structural insights of these gels were characterized by field-emission scanning electronic microscopy, atomic force microscopy, Fourier transform infrared analysis, and X-ray diffraction studies, and their mechanical strengths were characterized by rheological experiments. Both of the gels obtained from these two solvent systems were thermoreversible in nature, and these translucent gels had potential application for the treatment of waste water. The gel obtained from dipeptides with methanol-water was used to remove toxic dyes (crystal violet, Eriochrome Black T, and rhodamine B) from water. Furthermore, the gel obtained from dipeptide with assistance from toluene-petroleum ether was used as a phase-selective gelator for oil-spill recovery.

Chemically sulfated polysaccharides from natural sources: Assessment of extraction-sulfation efficiencies, structural features and antiviral activities.

The provisioning of compound libraries with a high degree of diversity and attractive pharmacological properties is a limiting step in drug development. This study reports the production of highly bioactive sulfated polysaccharides, originally present in a nonsulfated, dormant state in natural sources, and demonstrates their antiviral activity (human cytomegalovirus EC50 values of 2.34-7.77 µg/mL) at a low degree of cytotoxicity. Furthermore, data strongly suggested the inhibition of virus entry as the main mode of antiviral action. Remarkably, the utilized oleum-DMF reagent was able to generate a range of sulfated polysaccharides from various natural sources, possessing varying saccharide compositions, degrees of sulfation (0.4-1.7) and molecular masses (38-94,000 g/mol). Typically, in a matter of minutes, this reagent not only solubilized polysaccharides but also chemically converted their hydroxyl functionality into sulfates. The most active sulfated polysaccharide (EC50 of 2.62 µg/mL) proved to be a 94,000 g/mol branched glucan with sulfates at C-6/C-3,6/C-2,3,6 positions. In conclusion, the important determinants of such compounds' antiviral activity are: (i) degree of sulfation, (ii) molecular mass and (iii) structural features. Thus, our approach offers a huge prospect for the improvement of natural source-derived libraries based on biologically active polysaccharides with diversified chemical profiles.

Polysaccharides from Thymus vulgaris leaf: Structural features, antioxidant activity and interaction with bovine serum albumin.

Thymus vulgaris is used for various health benefits and culinary, nevertheless, report on its macromolecules is absent. Here, we report chemical compositions of the polysaccharides isolated from its leaf by sequential extraction with inorganic solvents. In particular, chemical profile of a unique rhamnogalacturonan I type polysaccharide containing ester linked phenolic acids has been described. Sugar compositional, TLC, UV-spectrometric and ESI-MS analyses of oligosaccharides generated from this polysaccharide by enzyme digestion, controlled acid hydrolysis and Smith degradation revealed atypical fine structural details. Biochemical analysis demonstrated dose-dependent antioxidant activity. A combination of large neutral side chains of the ramified region and ester linked phenolic acids are regarded as the functional sites. Ultraviolet spectrometric and fluorimetric analyses showed that this polysaccharide forms a homogeneous water-soluble complex with bovine serum albumin (binding constant, K = 2.91 × 106/M). Consequently, water extraction affords a polysaccharide which induces pharmacological effect; this underlines the impact of thyme as natural dietetic antioxidant.

Porphyrin-Gold Nanomaterial for Efficient Drug Delivery to Cancerous Cells.

With an aim to overcome multidrug resistance (MDR), nontargeted delivery, and drug toxicity, we developed a new nanochemotherapeutic system with tetrasodium salt of meso-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) armored on gold nanoparticles (TPPS-AuNPs). The nanocarrier is able to be selectively internalized within tumor cells than in normal cells followed by endocytosis and therefore delivers the antitumor drug doxorubicin (DOX) particularly to the nucleus of diseased cells. The embedment of TPPS on the gold nanosurface provides excellent stability and biocompatibility to the nanoparticles. Porphyrin interacts with the gold nanosurface through the coordination interaction between gold and pyrrolic nitrogen atoms of the porphyrin and forms a strong association complex. DOX-loaded nanocomposite (DOX@TPPS-AuNPs) demonstrated enhanced cellular uptake with significantly reduced drug efflux in MDR brain cancer cells, thereby increasing the retention time of the drug within tumor cells. It exhibited about 9 times greater potency for cellular apoptosis via triggered release commenced by acidic pH. DOX has been successfully loaded on the porphyrin-modified gold nanosurface noncovalently with high encapsulation efficacy (∼90%) and tightly associated under normal physiological conditions but capable of releasing ∼81% of drug in a low-pH environment. Subsequently, DOX-loaded TPPS-AuNPs exhibited higher inhibition of cellular metastasis, invasion, and angiogenesis, suggesting that TPPS-modified AuNPs could improve the therapeutic efficacy of the drug molecule. Unlike free DOX, drug-loaded TPPS-AuNPs did not show toxicity toward normal cells. Therefore, higher drug encapsulation efficacy with selective targeting potential and acidic-pH-mediated intracellular release of DOX at the nucleus make TPPS-AuNPs a "magic bullet" for implication in nanomedicine.

Chemical profile of a polysaccharide from Psidium guajava leaves and it's in vivo antitussive activity.

Decoction of Psidium guajava leaves has been used as medication for chronic coughs and breathlessness for ages. Despite demonstration of antitussive activity, the specific molecule responsible for this remains unidentified. Herein, we report chemical profile and antitussive activity of its water extract (WE) and a polysaccharide (F1) present therein. This polysaccharide (F1), purified from WE by precipitation with ethanol and then through Cu(II)acetate, contains Ara, Gal, Rha, Glc and GalA residues, and has a molecular mass of 156 kDa. It comprises of terminal-, (1,5)- and (1,3,5)-linked Araf; (1,3)-, (1,6)- and (1,3,6)-linked Galp alongside (1,2)- and (1,2,4)-linked Rhap residues. Oligosaccharides indicating polysaccharide structure have been generated by Smith degradation and characterized. The WE fraction suppressed citric acid induced cough efforts in guinea pigs in the dose of 50 mg kg-1. Assessment of antitussive activity of fractions prepared from WE namely F1 (polysaccharide) and F2 (ethanol soluble fraction) revealed that polysaccharide is the active component. Remarkably, tested samples do not alter the specific airway smooth muscle reactivity in animals significantly. The simple extraction method, prominent activity and favorable reactions profile suggest that this macromolecule could be an antitussive drug candidate.

Structural insight of an antioxidative arabinogalactan protein of Aegle marmelos fruit gum and it's interaction with ß-lactoglobulin.

The complication of arabinogalactan protein (AGP) structure, a significant ingredient of gum polysaccharides, not merely hinders the allocation of its role, but restricts its utilization as well. Here, we describe structural details of an AGP purified from Aegle marmelos fruit gum. This AGP (310×103g/mol), which is water-soluble, contains ß-1,3-linked galactopyranosyl main chain substituted at O-6 position with side chains containing galactose and arabinose residues. Also data on sugar composition, ring size, glycosidic linkage pattern, anomeric configuration and sequence of monosaccharide units of a number of oligosaccharides produced from this AGP by chemical and enzymatic methods were acquired. Biochemical analysis reveals resemblance in antioxidative potential between this arabinogalactan protein and standard antioxidants. Moreover, mixture of AGP and ß-lactoglobulin form stable water soluble complex having binding constant K=2.38×106/M. As gum polysaccharides are important raw materials of food industry discovering an antioxidative gum with the ability of creating stable water soluble complex with ß-lactoglobulin may have important implication.

Isolation and structural elements of a water-soluble free radical scavenger from Nyctanthes arbor-tristis leaves.

The leaves of Nyctanthes arbor-tristis L. (Oleaceae) are used in Ayurvedic medicine for the management of a range of diseases, but reports on its phytochemicals and pharmacological properties are inadequate. Herein, we report purification of an antioxidative polysaccharide (F2) extracted from its leaves by water. The presence of a highly branched polysaccharide (75 kDa) containing esterified phenolic acids was revealed by chemical, chromatographic and spectroscopic analyses. Particularly, ESMS analysis of per acetylated oligomeric fragments derived by Smith degradation provides important structural information on a spectrum of glycerol tagged oligosaccharides. This polysaccharide showed dose dependent free radical scavenging capacity as evidenced by DPPH and Ferric reducing power assay. This pharmacologically active compound (F2) formed a water soluble complex with bovine serum albumin over pH 4.0-7.4. Accordingly, traditional aqueous extraction method provides a molecular entity that induces a pharmacological effect: this could epitomize a smart approach in phytotherapeutic management.