Table of Contents

Abstract: The crude methanol extract of the dried aerial parts of Siegesbeckia glabrescens (Compositae) showed antibacterial activity against the foodborne pathogen Staphylococcus aureus. Bioactivity-guided separation led to the isolation of 3-(dodecanoyloxy)-2-(isobutyryloxy)-4-methylpentanoic acid from nature for the first time. The structure was determined by spectroscopic data analysis (UV, MS, and NMR). The minimal inhibitory concentration (MIC) of 3-(dodecanoyloxy)-2-(isobutyryloxy)-4-methylpentanoic acid against S. aureus was found to be 3.12 μg/mL. In addition, in a further antimicrobial activity assay against Gram-positive (B. subtilis, E. faecalis, P. acnes, S. epidermidis, S. schleiferi subsp. coagulans, S. agalactiae and S. pyrogens), and Gram-negative bacteria (E. coli and P. aeruginosa), and yeast strains (C. alibicans and F. neoformans), the antimicrobial activity of the compound was found to be specific for Gram-positive bacteria. The MIC values of the compound for Gram-positive bacteria ranged from 3.12 to 25 mg/mL. Furthermore, it was found that the 2-(isobutyryloxy)-4-methylpentanoic acid substituent may operate as a key factor in the antibacterial activity of the compound, together with the laurate group.

Abstract: The widespread use of β-lactam antibiotics has led to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to β-lactams by two main mechanisms: the production of β-lactamases, sometimes accompanied by a decrease of outer membrane permeability, and the production of low-affinity, drug resistant Penicillin Binding Proteins (PBPs). PBPs remain attractive targets for developing new antibiotic agents because they catalyse the last steps of the biosynthesis of peptidoglycan, which is unique to bacteria, and lies outside the cytoplasmic membrane. Here we summarize the “current state of the art” of non-β-lactam inhibitors of PBPs, which have being developed in an attempt to counter the emergence of β-lactam resistance. These molecules are not susceptible to hydrolysis by β-lactamases and thus present a real alternative to β-lactams. We present transition state analogs such as boronic acids, which can covalently bind to the active serine residue in the catalytic site. Molecules containing ring structures different from the β-lactam-ring like lactivicin are able to acylate the active serine residue. High throughput screening methods, in combination with virtual screening methods and structure based design, have allowed the development of new molecules. Some of these novel inhibitors are active against major pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and thus open avenues new for the discovery of novel antibiotics.

Abstract: A straightforward method has been developed for the synthesis of the benzimidazole ring system through a carbon-nitrogen cross-coupling reaction. In the presence of 2.0 equiv. of K₂CO₃ in water at 100 °C for 30 h, the intramolecular cyclization of N-(2-iodoaryl)benzamidine provides benzimidazole derivatives in moderate to high yields. Remarkably, the procedure occurs exclusively in water and doesn’t require the use of any additional reagent/catalyst, rendering the methodology highly valuable from both environmental and economical points of view.

Abstract: Acridocarpus orientalis (AO) is a traditional medicinal plant used for treatment of inflammatory diseases that may have potential in cancer treatment. In the present study, the aqueous ethanolic crude extract of Acridocarpus aerial parts obtained from Al Ain and Oman were evaluated for their antioxidant capability, polyphenolic content, anti-lipoxygenase and anti-histone deacetylase (HDAC) properties. The total antioxidant capacity was estimated by the FRAP, DPPH, ABTS and b-carotene bleaching assays. Acridocarpus-Al Ain exhibited the highest polyphenolic content (184.24 mg gallic acid/g) and the best antioxidant activity (1.1, 1.04, 1.14 mmol ascorbic acid equivalent/g in the FRAP, ABTS and DPPH assays, respectively). Additionally, the same extract showed significant anti-inflammatory properties via lipoxygenase (LOX) inhibitory activity (IC₅₀ = 50.58 µg/mL). Acridocarpus-Al Ain also showed the strongest histone deacetylase (HDACs) inhibitory activity (IC₅₀ = 93.28 µg/mL). The results reported here suggest that there was a significant influence of location and the plant may be considered a good source of compounds with antioxidant, anti-LOX and HDAC properties for therapeutic, nutraceutical and functional food applications.

Abstract: Cystine-knot peptides display exceptional structural, thermal, and biological stability. Their eponymous motif consists of six cysteine residues that form three disulfide bonds, resulting in a notably rigid structural core. Since they highly tolerate either rational or combinatorial changes in their primary structure, cystine knots are considered to be promising frameworks for the development of peptide-based pharmaceuticals. Despite their relatively small size (two to three dozens amino acid residues), the chemical synthesis route is challenging since it involves critical steps such as head-to-tail cyclization and oxidative folding towards the respective bioactive isomer. Herein we describe the topology of cystine-knot peptides, their synthetic availability and briefly discuss potential applications of engineered variants in diagnostics and therapy.

Abstract: The heterocyclic C15 apocarotenoid 1 was isolated from mated cultures of the strains F986 (+) and F921 (−) of Blakeslea trispora. This new compound formed during sexual interaction is a minor constituent of the culture media and its structure was elucidated by spectroscopic data, including 2D-NMR. A plausible biosynthetic pathway involving a double degradation of β-carotene, followed by several oxidations of the resulting monocyclofarnesane C15 fragment is proposed.

Abstract: Solanum guaraniticum is a shrub belonging to the Solanaceae family popularly known in Brazil as jurubeba or false-jurubeba. The aim of this study was to evaluate the antioxidant activity of crude extract and chloroform, ethyl acetate and n-butanol fractions from its leaves, verifying the ability to remove reactive species and identify and quantify phenolic compounds. The ethyl acetate fraction showed the highest amount of total polyphenols (546.57 ± 2.35 mg gallic acid equivalent/g) and the lowest IC₅₀ (9.11 ± 0.75 µg/mL) by the DPPH method. Furthermore, the chloroform fraction presented the highest content of flavonoids (75.73 ± 0.34 mg rutin equivalents/g), tannins (56.03 ± 0.68 mg catechin equivalents/g) and alkaloids (10.79 ± 0.06 mg/g). This fraction was effective in the scavenging of reactive species by 2′,7′-dichlorofluorescein diacetate assay, in addition to completely reducing protein carbonyl content and reducing lipid peroxidation at basal levels even at low concentrations. Chlorogenic, caffeic and rosmarinic acids were identified and quantified by HPLC/DAD. These results show that S. guaraniticum is rich in phenolic compounds and has potential as an antioxidant.

Abstract: Enhanced ganoderic acid Me (GA-Me, an important anti-tumor triterpene) yield was attained with the medicinal fungus Ganoderma lucidum using response surface methodology (RSM). Interactions were studied with three variables, viz. glucose, peptone and culture time using a Central Composite Design (CCD). The CCD contains a total of 20 experiments with the first 14 experiments organized in a fractional factorial design, with the experimental trails from 15 to 20 involving the replications of the central points. A polynomial model, describing the relationships between the yield of GA-Me and the three factors in a second-order equation, was developed. The model predicted the maximum GA-Me yield of 11.9 mg·L⁻¹ for glucose, peptone, culture time values of 44.4 g·L⁻¹, 5.0 g·L⁻¹, 437.1 h, respectively, and a maximum GA-Me yield of 12.4 mg·L⁻¹ was obtained in the validation experiment, which represented a 129.6% increase in titre compared to that of the non-optimized conditions. In addition, 11.4 mg·L⁻¹ of GA-Me was obtained in a 30-L agitated fermenter under the optimized conditions, suggesting the submerged culture conditions optimized in the present study were also suitable for GA-Me production on a large scale.

Abstract: A novel poly(acrylic acid-co-acrylamide)AlZnFe₂O₄/potassium humate superabsorbent hydrogel nanocomposite (PHNC) was synthesized and its physical properties characterized using SEM, Energy Dispersive X-ray (EDX) and FTIR spectroscopic techniques. Air dried sandy loam soil was amended with 0.1 to 0.4 w/w% of PHNC to evaluate its soil moisture retention attributes. Effect of PHNC amendment on pH, electrical conductivity (EC), porosity, bulk density and hydraulic conductivity of sandy loam soil was also studied. The soil amendment with 0.1 to 0.4 w/w% of PHNC remarkably enhanced the moisture retention at field capacity as compared to the un-amended soils. Seed germination and seedling growth of wheat (Triticum aestivum L.) was considerably increased and a delay by 6–9 days in wilting of seedlings was observed in the soil amended with PHNC, resulting in improved wheat plant establishment and growth.

Abstract: Five terpenoids were tested by the macrodilution broth method to determine their inhibition activity on cariogenic bacterial growth. In general, α-, β-amyrin and α-amyrin phenylacetate proved to be active, reducing the bacterial viability to less than 20%.

Abstract: A sequential solvent extraction scheme was employed for the extraction of antioxidant compounds from kenaf (Hibiscus cannabinus L.) seeds. Yield of extracts varied widely among the solvents and was the highest for hexane extract (16.6% based on dry weight basis), while water extract exhibited the highest total phenolic content (18.78 mg GAE/g extract), total flavonoid content (2.49 mg RE/g extract), and antioxidant activities (p < 0.05). DPPH and hydroxyl radical scavenging, β-carotene bleaching, metal chelating activity, ferric thiocyanate and thiobarbituric acid reactive substances assays were employed to comprehensively assess the antioxidant potential of different solvent extracts prepared sequentially. Besides water, methanolic extract also exhibited high retardation towards the formation of hydroperoxides and thiobarbituric acid reactive substances in the total antioxidant activity tests (p < 0.05). As conclusion, water and methanol extracts of kenaf seed may potentially serve as new sources of antioxidants for food and nutraceutical applications.

Abstract: Two novel trivalent antimony(III) and bismuth(III) complexes with the nitrogen-donor heterocyclic ligand dipyrido[3,2-a:2',3'-c]phenazine (dppz) were synthesized and characterized as [Sb(dppz)Cl₃]∙H₂O∙CH₃OH and [Bi(dppz)Cl₃]. The crystal structure of Sb(III) complex was determined by X-ray crystallography. These complexes were evaluated for their activity against the promastigote form of Sb(III)-sensitive and –resistant Leishmania infantum chagasi and Leishmania amazonensis strains. Both complexes were more effective than dppz alone in inhibiting the growth of Leishmania promastigotes and were at least 77 and 2,400 times more active than potassium antimonyl tartrate in Sb(III)-sensitive and -resistant Leishmania, respectively. The cytotoxicity of dppz and its complexes against mouse peritoneal macrophages occurred at dppz concentrations at least 6-fold greater than those found to be active against Leishmania promastigotes.To investigate the role of the metal in the improved antileishmanial activity of dppz, the activity of the Sb(III) complex was compared between the Sb-resistant mutants and their respective parental sensitive strains. The lack of cross-resistance to the Sb(III)-dppz complex together with the much lower activity of antimonyl tartrate, SbCl₃ and BiCl₃ strongly support the model that the metal is not active by itself but improves the activity of dppz through complexation.

Abstract: Two novel compounds, 1α-methoxy-3β-hydroxy-4α-(3′,4′-dihydroxyphenyl)-1, 2,3,4-tetrahydronaphthalin (1) and 1α,3β-dihydroxy-4α-(3′,4′-dihydroxyphenyl)-1,2,3,4-tetrahydronaphthalin (2), were isolated along with six known compounds 3–8 from the rhizomes of Cyperus rotundus. This paper reports the isolation and full spectroscopic characterization of these new compounds by NMR, UV, IR and MS data.

Abstract: Chemical investigation of two species of marine ascidians, Aplidium elegans and Ciona edwardsii, collected in Mediterranean area, led to isolation of a series of alkyl sulfates (compounds 1–5) including three new molecules 1–3. Structures of the new metabolites have been elucidated by spectroscopic analysis. Based on previously reported cytotoxic activity of these type of molecules, compounds 1–3 have been tested for their effects on the growth of two cell lines, J774A.1 (BALB/c murine macrophages) and C6 (rat glioma) in vitro. Compounds 1 and 2 induced selective concentration-dependent mortality on J774A.1 cells.

Abstract: To study the chemical constituents of the fruits of noni (Morinda citrifolia L.), and find novel compounds, an n-butanol extract of the ethanol soluble fraction was subjected to repeated silica gel and ODS column chromatography and HPLC. Two new glycosides were isolated and their structures elucidated by NMR and HRFAB-MS spectrometry as (2E,4E,7Z)-deca-2,4,7-trienoate-2-O-β-D-glucopyranosyl-β-D-glucopyra-noside (1) and amyl-1-O-β-D-apio-furanosyl-1,6-O-β-D-glucopyranoside (2), respectively.

Abstract: Phenolic compounds are known to have antioxidant capacity; however, there is little information about molecular interactions between particular phenolics found in fruits at different developmental stages. Therefore, the total antioxidant capacity of the phenolic compounds of a fruit may not correspond to the sum of individual antioxidant capacity given by antioxidants from that tissue. In this study, individual antioxidant capacity and the interactions of four major phenolic compounds (chlorogenic, gallic, protocatechuic and vanillic acid) found in ‘Ataulfo’ mango pulp were tested using the DPPH assay. Significant synergism was found in the majority of the all combinations, as well as the combination of the four phenolics. However, antagonism was also observed between some molecules. This work demonstrated particular interactions that may occur in a complex environment within the complex framework of a natural food. The present results may also assist in the future design of functional foods or ingredients based on their antioxidant activity and their synergistic or antagonist interactions.

Abstract: There is considerable attention directed at chemically modifying nucleic acids with robust functional groups in order to alter their properties. Since the breakthrough of copper-assisted azide-alkyne cycloadditions (CuAAC), there have been several reports describing the synthesis and properties of novel triazole-modified nucleic acid derivatives for potential downstream DNA- and RNA-based applications. This review will focus on highlighting representative novel nucleic acid molecular structures that have been synthesized via the “click” azide-alkyne cycloaddition. Many of these derivatives show compatibility for various applications that involve enzymatic transformation, nucleic acid hybridization, molecular tagging and purification, and gene silencing. The details of these applications are discussed. In conclusion, the future of nucleic acid analogues functionalized with triazoles is promising.

Abstract: A series of novel dispirooxindoles have been synthesized through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the decarboxylative condensation of isatin and an α-amino acid with the dipolarophile 5-benzylidene-1,3-dimethylpyrimidine-2,4,6-trione. This method has the advantages of mild reaction conditions, high atom economy, excellent yields, and high regio- and stereo-selectivity.

Abstract: Bis(acetoxy)iodobenzene and related acyloxy derivatives of hypervalent I(III) were studied by variable temperature solution-state ¹⁷O-NMR and DFT calculations. The ¹⁷O-NMR spectra reveal a dynamic process that interchanges the oxygen atoms of the acyloxy groups. For the first time, coalescence events could be detected for such compounds, allowing the determination of activation free energy data which are found to range between 44 and 47 kJ/mol. The analysis of the ¹⁷O linewidth measured for bis(acetoxy)iodobenzene indicates that the activation entropy is negligible. DFT calculations show that the oxygen atom exchange arises as a consequence of the [1,3]-sigmatropic shift of iodine. The calculated activation barriers are in excellent agreement with the experimental results. Both the ¹⁷O-NMR and DFT studies show that the solvent and chemical alterations, such as modification of the acyl groups or para- substitution of the benzene ring, hardly affect the energetics of the dynamic process. The low I-O Wiberg bond index (0.41–0.42) indicates a possible explanation of the invariance of both the energy barrier and the ¹⁷O chemical shift with para-substitution.

Abstract: The purpose of this work was the synthesis, characterization and efficacy evaluation of new biocompatible antioxidant polymers linking trans-ferulic acid or a-lipoic acid. In particular, ferulic or lipoic acid were introduced in the preformed polymeric backbone. The new antioxidant biopolymers were characterized by Fourier transform infrared spectroscopy and gel permeation chromatography. The degree of functionalization (moles of antioxidant per gram of polymer) was determined by the Gaur-Gupta method for free amino group determination and by the Folin method for the phenolic groups. Their ability to inhibit lipid peroxidation were estimated in rat liver microsomal membranes induced in vitro by tert-BOOH (tert-butyl hydroperoxide), as a source of free radicals. The DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging effect was also evaluated. The obtained systems, with different solubility, showed strong antioxidant and antiradical activities, suggesting potential use as packaging materials for foods, cosmetics, pharmaceuticals and personal care products. Moreover, the cytotoxicity of the synthesized polymers was also evaluated on Caco-2 cell cultures in order to verify their biocompatibility when exposed to an absorptive epithelial cell line.

Abstract: To elucidate the underlying mechanism of cardio-protective activity of the total ginsenosides (TGS) of Radix Ginseng, proteomic analysis using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-TOF-MS techniques was employed for identifying the underlying targets of TGS on improvement of the energy metabolism of isolated rat heart tissues perfused in Langendorff system under ischemia-reperfusion injury conditions. The image analysis results revealed 11 differentially expressed proteins in the TGS-treated heart tissues; these proteins, including LDHB and ODP-2, were found to be closely related to the function of tricarboxylic acid (TCA) cycle that plays pivotal roles in cardiac energy metabolism. It is thus concluded that improvement of cardiac energy metabolism via activating proteins in TCA cycle could be the major action pathway and targets of TGS activity against rat heart tissue injury.

Abstract: N^ε-(carboxymethyl) lysine (CML) is the most abundant advanced glycation end product (AGE), and frequently selected as an AGEs marker in laboratory studies. In this paper, the formation and inhibition of N^ε-(carboxymethyl)lysine in saccharide-lysine model systems during microwave heating have been studied. The microwave heating treatment significantly promoted the formation of CML during Maillard reactions, which was related to the reaction temperature, time and type of saccharide. The order of CML formation for different saccharides was lactose > glucose > sucrose. Then, the inhibition effect on CML by five inhibitors was further examined. According to the results, ascorbic acid and tocopherol did not affect inhibition of CML, in contrast, thiamin, rutin and quercetin inhibited CML formation, and the inhibitory effects were concentration dependent.

Abstract: This review summarizes human infections caused by endoparasites, including protozoa, nematodes, trematodes, and cestodes, which affect more than 30% of the human population, and medicinal plants of potential use in their treatment. Because vaccinations do not work in most instances and the parasites have sometimes become resistant to the available synthetic therapeutics, it is important to search for alternative sources of anti-parasitic drugs. Plants produce a high diversity of secondary metabolites with interesting biological activities, such as cytotoxic, anti-parasitic and anti-microbial properties. These drugs often interfere with central targets in parasites, such as DNA (intercalation, alkylation), membrane integrity, microtubules and neuronal signal transduction. Plant extracts and isolated secondary metabolites which can inhibit protozoan parasites, such as Plasmodium, Trypanosoma, Leishmania, Trichomonas and intestinal worms are discussed. The identified plants and compounds offer a chance to develop new drugs against parasitic diseases. Most of them need to be tested in more detail, especially in animal models and if successful, in clinical trials.

Abstract: DNA as a Chiral Scaffold for Asymmetric Synthesis

Abstract: Homogenous bis-sulfonic acid ionic liquids (1 mol equiv.) in DMSO (10 mol equiv.) at 100 °C efficiently mediated the conversion of D-fructose into 5-hydroxymethyl-2-furfural in 75% isolated yield, which was roughly a 10% increment compared to the case of the mono-sulfonic acid ionic liquids.

Abstract: The increasing emergence especially of drug-resistant tuberculosis has led to a strong demand for new anti-tuberculosis drugs. Eighteen salicylanilide benzoates were evaluated for their inhibition potential against Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii; minimum inhibitory concentration values ranged from 0.5 to 16 μmol/L. The most active esters underwent additional biological assays. Four benzoates inhibited effectively the growth of five multidrug-resistant strains and one extensively drug-resistant strain of M. tuberculosis at low concentrations (0.25–2 μmol/L) regardless of the resistance patterns. The highest rate of multidrug-resistant mycobacteria inhibition expressed 4-chloro-2-[4-(trifluoromethyl)-phenylcarbamoyl]phenyl benzoate (0.25–1 μmol/L). Unfortunately, the most potent esters were still considerably cytotoxic, although mostly less than their parent salicylanilides.

Abstract: The Kabachnik–Fields (phospha-Mannich) reaction involving the condensation of primary or secondary amines, oxo compounds (aldehydes and ketones) and >P(O)H species, especially dialkyl phosphites, represents a good choice for the synthesis of α-aminophosphonates that are of significant importance due to their biological activity. In general, these three-component reactions may take place via an imine or an α-hydroxy-phosphonate intermediate. The monitoring of a few Kabachnik–Fields reactions by in situ Fourier transform IR spectroscopy has indicated the involvement of the imine intermediate that was also justified by theoretical calculations. The Kabachnik–Fields reaction was extended to >P(O)H species, comprising cyclic phosphites, acyclic and cyclic H-phosphinates, as well as secondary phosphine oxides. On the other hand, heterocyclic amines were also used to prepare new α-amino phosphonic, phosphinic and phosphine oxide derivatives. In most cases, the synthesis under solvent-free microwave (MW) conditions is the method of choice. It was proved that, in the cases studied by us, there was no need for the use of any catalyst. Moreover, it can be said that sophisticated and environmentally unfriendly catalysts suggested are completely unnecessary under MW conditions. Finally, the double Kabachnik–Fields reaction has made available bis(phosphonomethyl)amines, bis(phosphinoxidomethyl)amines and related species. The bis(phosphinoxidomethyl)amines serve as precursors for bisphosphines that furnish ring platinum complexes on reaction with dichlorodibenzonitriloplatinum.

Abstract: Tilapia frame protein was hydrolyzed by different proteases, including properase E, pepsin, trypsin, flavourzyme, neutrase, gc106 and papain, to obtain antioxidant peptides. The tilapia frame protein hydrolysate (TFPH) obtained by trypsin exhibited the highest degree of hydrolysis and antioxidant activity. Three series of peptides (TFPH1, TFPH 2 and TFPH 3) were obtained by ultrafiltration of TFPH through molecular weight cut-off membranes of 5, 3 and 1 kDa, respectively, and their IC₅₀ values on scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide anion radical (^•O₂), hydrogen peroxides (H₂O₂) and hydroxyl radical (•OH) activities were determined and compared with glutathione (GSH). The results showed that TFPH1 had the highest antioxidant activity. TFPH1 was further purified using ion exchange chromatography, gel filtration chromatography, and reversed phase high performance liquid chromatography (RP-HPLC). Finally, two antioxidant peptides were identified and the amino acid sequences were identified as Asp-Cys-Gly-Tyr (456.12 Da) and Asn-Tyr-Asp-Glu-Tyr (702.26 Da), respectively. The IC₅₀ values of two peptides on hydroxyl radical scavenging activity were 27.6 and 38.4 μg/mL, respectively.

Abstract: In this study, the total phenolic and flavonoid contents, the 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging ability and the ferric reducing power (FRAP) of Aloe vera were measured to determine the antioxidant activity of this species. The in vivo antidiabetic effects of the plant were also investigated using streptozotocin-induced type 2 diabetic model rats that were divided into five groups based on the treatment received: (1) water (WC); (2) glibenclamide; (3) concentrated gel extract (Gel-C); (4) ethanol (80%) gel extract (Gel-Et); and (5) ethanol (80%) skin extract of Aloe vera (Skin-Et). Skin-Et, which contained the highest level of total phenolics (62.37 ± 1.34 mg_{gallic acid}/kg) and flavonoids (20.83 ± 0.77 mg/kg), exhibited the highest scavenging activity (85.01 ± 0.52%) and the greatest reducing power (185.98 ± 0.41 µM), indicating that the skin contained the highest level of antioxidants. The oral consumption of Gel-Et for 4 weeks a caused significant reduction in the fasting serum glucose levels of the rats. The rats in the Gel-C-, Gel-Et- and Skin-Et-treated groups experienced a reduction in their total cholesterol levels by 11%, 17% and 25%, respectively and a reduction in their LDL cholesterol levels by 45%, 3% and 69%, respectively. The in vivo experimental antioxidant parameter MDA is strongly correlated with the in vitro antioxidant parameters of flavonoids and polyphenols, namely the DPPH and FRAP values (r = 0.94, 0.92, 0.93, 0.90), thus confirming the antioxidant potential of the Aloe vera extracts.

Abstract: Diabetic retinopathy is a complex disease that potentially involves increased production of advanced glycosylation end products (AGEs) and elevated aldose reductase (AR) activity, which are related with oxidative stress and inflammation. The aim of this study was to investigate the effects of hesperidin on retinal and plasma abnormalities in streptozotocin-induced diabetic rats. Hesperidin (100, 200 mg/kg daily) was given to diabetic rats for 12 weeks. The blood-retina breakdown (BRB) was determined after 2 weeks of treatment followed by the measurement of related physiological parameters with ELISA kits and immunohistochemistry staining at the end of the study. Elevated AR activity and blood glucose, increased retinal levels of vascular endothelial growth factor (VEGF), ICAM-1, TNF-α, IL-1β and AGEs as well as reduced retina thickness were observed in diabetic rats. Hesperidin treatment significantly suppressed BRB breakdown and increased retina thickness, reduced blood glucose, AR activity and retinal TNF-α, ICAM-1, VEGF, IL-1β and AGEs levels. Furthermore, treatment with hesperidin significantly reduced plasma malondialdehyde (MDA) levels and increased SOD activity in diabetic rats. These data demonstrated that hesperidin attenuates retina and plasma abnormalities via anti-angiogenic, anti-inflammatory and antioxidative effects, as well as the inhibitory effect on polyol pathway and AGEs accumulation.

Abstract: A new series of asymmetrically N,N'-substituted ureas 20–25 was prepared using solvent free conditions, which is an eco-friendly methodology, starting with Schiff bases derived from cinnamaldehyde and p-substituted anilines, which are subsequently submitted to reduction reactions that afford the corresponding asymmetric secondary amines. All of the intermediates were prepared using solvent free reactions, which were compared to traditional methodologies. All of the reactions required a remarkably short amount of time and provided good yields when solvent free conditions were employed compared to other methodologies. The DNA-topoisomerase II-α (topo II-α) activity was evaluated in relaxation assays, which showed that all of the compounds inhibited the enzyme activity at 10 μM, except for urea 24. Furthermore, a molecular docking study indicated that the compounds 20–25 binding to the topo II-α are able to interact with the same binding site as the anticancer drug etoposide, suggesting that the ureas could inhibit the enzyme by the same mechanism of action observed for etoposide, which prevents re-ligation of the DNA strands.

Abstract: Phytochemical research of two Tolpis species, T. proustii and T. lagopoda, led to the isolation of three new compounds: 30-chloro-3β-acetoxy-22α-hydroxyl-20(21)-taraxastene (1), 3β,22α-diacetoxy-30-ethoxy-20(21)-taraxastene (2) and 3β,28-dihydroxy-11α-hydroperoxy-12-ursene (3). The structures of the new compounds were elucidated by means of extensive IR, NMR, and MS data and by comparison of data reported in the literature. The in vitro antioxidant activities of the extracts were assessed by the DPPH and ABTS scavenging methods. The cytotoxicity of several known compounds and its derivatives was also assessed against human myeloid leukemia K-562 and K-562/ADR cell lines.

Abstract: Phenolic acids are potent antioxidants, yet the quantitative structure-activity relationships of phenolic acids remain unclear. The purpose of this study was to establish 3D-QSAR models able to predict phenolic acids with high DPPH• scavenging activity and understand their structure-activity relationships. The model has been established by using a training set of compounds with cross-validated q² = 0.638/0.855, non-cross-validated r² = 0.984/0.986, standard error of estimate = 0.236/0.216, and F = 139.126/208.320 for the best CoMFA/CoMSIA models. The predictive ability of the models was validated with the correlation coefficient r²_pred = 0.971/0.996 (>0.6) for each model. Additionally, the contour map results suggested that structural characteristics of phenolics acids favorable for the high DPPH• scavenging activity might include: (1) bulky and/or electron-donating substituent groups on the phenol ring; (2) electron-donating groups at the meta-position and/or hydrophobic groups at the meta-/ortho-position; (3) hydrogen-bond donor/electron-donating groups at the ortho-position. The results have been confirmed based on structural analyses of phenolic acids and their DPPH• scavenging data from eight recent publications. The findings may provide deeper insight into the antioxidant mechanisms and provide useful information for selecting phenolic acids for free radical scavenging properties.

Abstract: A high performance liquid chromatographic (HPLC) method with diode array detection (DAD) was established for simultaneous determination of seven main bioactive components in San-ao decoction and its series of formulae (San-ao decoction, Wu-ao decoction, Qi-ao decoction and Jia-wei San-ao decoction). Seven compounds were analyzed simultaneously with a XTerra C₁₈ column (4.6 mm × 250 mm, 5 µm) using a linear gradient elution of a mobile phase containing acetonitrile (A) and a buffer solution (0.02 mol/L potassium dihydrogen phosphate and adjusted to pH 3 using phosphoric acid) (B); the flow rate was 1.0 mL/min. The sample was detected with DAD at 210, 254 and 360 nm and the column was maintained at 30 °C. All the compounds showed good linearity (r² > 0.9984) in the tested concentration range. The precisions were evaluated by intra-day and inter-day tests, and relative standard deviation (R.S.D.) values within the range of 0.83%–2.53% and 0.64%–2.77% were reported, respectively. The recoveries of the quantified compounds were observed to cover a range from 95.34% and 104.82% with R.S.D. values less than 2.72%. The validated method was successfully applied for the simultaneous determination of seven main bioactive components including ephedrine (1), amygdalin (2), liquiritin (3), benzoic acid (4), isoliquiritin (5), formononetin (6) and glycyrrhizic acid (7) in San-ao decoction and its series of formulae. The results also showed a wide variation in the content of the identified active compounds in these samples, which could also be helpful to illustrate the drug interactions after some herbs combined in different formulations.

Abstract: Traditional or folk medicinal herbs continue to be prescribed in the treatment of various diseases and conditions in many cultures. Recent scientific efforts have focused on the potential roles of extracts of traditional herbs as alternative and complementary medications for cancer treatment. In Taiwan, Davallia divaricata Blume has been traditionally employed in folk medicine for therapy of lung cancer, davallic acid being the major active compound of D. divaricata Blume. In this study, we investigated the inhibitory activity of davallic acid on the proliferation of A549 lung cancer cells. Davallic acid was extracted from D. divaricata Blume, and its effects on cell viability, cell cycle distribution, ROS level, and apoptotic protein expression in A549 cells were determined. Davallic acid significantly induced reactive oxygen species (ROS) generation as well as caspase-3, -8, and -9 activation, thereby repressing A549 cell growth and elevating apoptotic activity. Since lung cancer has a high incidence of recurrence, these results indicate that davallic acid may have the potential to be a natural anti-lung cancer compound, and may provide a basis for further study of its use in combating cancer.

Abstract: Five novel isoquinoline alkaloids (+)-N-(methoxylcarbonyl)-N-nordicentrin (1), (+)-N-(methoxylcarbonyl)-N-norpredicentrine (2), (+)-N-(methoxylcarbonyl)-N-norbulbodione (3), and (+)-N-(methoxylcarbonyl)-N-norisocorydione (4), and (+)-8-methoxyisolaurenine-N- oxide (5) were isolated, together with one known compound, (+)-N-(methoxylcarbonyl)- N-norglaucine (6), from a 70% EtOH extract of the barks of Litsea cubeba. Structural elucidation of all the compounds were performed by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. Alkaloids 1, 2 and 6 showed antimicrobial activity against the bacterium S. aureus and two fungi (A. alternata and C. nicotianae). Compounds 3,4 exhibited significant cytotoxicity against all of six tested tumor cell lines.

Abstract: Leishmaniasis is a neglected disease responsible for about 56,000 deaths every year. Despite its importance, there are no effective, safe and proper treatments for leishmaniasis due to strain resistance and/or drug side-effects. In this work we report the synthesis, molecular modeling, cytotoxicity and the antileishmanial profile of a series of 4-(1H-pyrazol-1-yl)benzenesulfonamides. Our experimental data showed an active profile for some compounds against Leishmania infantum and Leishmania amazonensis. The profile of two compounds against L. infantum was similar to that of pentamidine, but with lower cytotoxicity. Molecular modeling evaluation indicated that changes in electronic regions, orientation as well as lipophilicity of the derivatives were areas to improve the interaction with the parasitic target. Overall the compounds represent feasible prototypes for designing new molecules against L. infantum and L. amazonensis.

Abstract: Radiopharmaceuticals are employed in patient diagnostics and disease treatments. Concerning the diagnosis aspect, technetium-99m (^99mTc) is utilized to label radiopharmaceuticals for single photon computed emission tomography (SPECT) due to its physical and chemical characteristics. ^99mTc fixation on pharmaceuticals depends on a reducing agent, stannous chloride (SnCl₂) being the most widely-utilized. The genotoxic, clastogenic and anegenic properties of the ^99mTc-MDP(methylene diphosphonate used for bone SPECT) and SnCl₂ were evaluated in Wistar rat blood cells using the Comet assay and micronucleus test. The experimental approach was to endovenously administer NaCl 0.9% (negative control), cyclophosphamide 50 mg/kg b.w. (positive control), SnCl₂ 500 μg/mL or ^99mTc-MDP to animals and blood samples taken immediately before the injection, 3, and 24 h after (in the Comet assay) and 36 h after, for micronucleus test. The data showed that both SnCl₂ and ^99mTc-MDP-induced deoxyribonucleic acid (DNA) strand breaks in rat total blood cells, suggesting genotoxic potential. The ^99mTc-MDP was not able to induce a significant DNA strand breaks increase in in vivo assays. Taken together, the data presented here points to the formation of a complex between SnCl₂ in the radiopharmaceutical ^99mTc-MDP, responsible for the decrease in cell damage, compared to both isolated chemical agents. These findings are important for the practice of nuclear medicine.

Abstract: The purpose of this work was to research the enhancement of Epimedium fried with suet oil based on the in vivo formation self-assembled flavonoid nanomicelles. Taking icariin as the representative, under the action of suet oil, self-assembled nanomicelles were prepared under simulated gastrointestinal tract conditions and were characterized by dynamic light scattering and transmission electron microscopy (TEM). The experiments with icariin self-assembled nanomicelles without suet oil were done according to the above. The influence of suet oil on the transportation of icariin across Caco-2 cell monolayers and the absorption in rat intestine of self-assembled nanomicelles were evaluated. The particle size of icariin self-assembled nanomicelles with suet oil was smaller than without suet oil. The nanomicelles seemed to be monodisperse spherical particle with smooth surfaces. The icariin entrapment efficiency of self-assembled nanomicelles with suet oil was increased from 43.1% to 89.7%. In Caco-2 cell monolayers, the absorptive permeability, secretory permeability and efflux ratio of icariin self-assembled nanomicelles with suet oil was 1.26 × 10^{−6 cm/s, 5.91 × 10−6 cm/s and 4.69, respectively, while that of icariin self-assembled nanomicelles without suet oil was 0.62 × 10−6 cm/s, 3.00 × 10−6} cm/s, and 4.84, respectively. In rat intestinal perfusion experiments, the permeability coefficient of icariin self-assembled nanomicelles with suet oil in duodenum was higher than the value of icariin self-assembled nanomicelles without suet oil (p < 0.05). With the action of suet oil, icariin self-assembled nanomicelles were more stable and the entrapment efficiency was higher than that without suet oil, which could increase the solubility of icariin and improve its intestinal absorption. Therefore, suet oil plays a role in its enhancement.

Abstract: Quercetin is a well-known antioxidant. Here, we investigated the effects of treatment with quercetin on mean arterial pressure (MAP), heart rate (HR) and baroreflex sensitivity (BRS) in spontaneously hypertensive rats (SHR). SHR and their controls (WKY) were orally treated with quercetin (2, 10 or 25 mg/kg/day) or saline for seven days. On the 8th day, MAP and HR were recorded. BRS was tested using phenylephrine (8 mg/kg, i.v.) and sodium nitroprusside (25 mg/kg, i.v.). Oxidative stress was measured by tiobarbituric acid reactive species assay. The doses of 10 (n = 8) and 25 mg/kg (n = 8) were able to decrease the MAP in SHR (n = 9) (163 ± 4 and 156 ± 5 vs. 173 ± 6, respectively, p < 0.05) but not in WKY (117 ± 1 and 118 ± 2 vs. 113 ± 1, respectively, p < 0.05). The dose of 25 mg/kg/day increased the sensitivity of parasympathetic component of the baroreflex (−2.47 ± 0.31 vs. −1.25 ± 0.8 bpm/mmHg) and decreased serum oxidative stress in SHR (2.04 ± 0.17 vs. 3.22 ± 0.37 nmol/mL, n = 6). Our data suggest that treatment with quercetin reduces hypertension and improves BRS in SHR via reduction in oxidative stress.

Abstract: Natural products contribute significantly to available drug therapies and have been a rich source for scientific investigation. In general, due to their low cost and traditional use in some cultures, they are an object of growing interest as alternatives to synthetic drugs. With several diseases such as cancer, and inflammatory and neuropathic diseases having been linked to the participation of purinergic (P2) receptors, there has been a flurry of investigations on ligands within natural products. Thirty-four different sources of these compounds have been found so far, that have shown either agonistic or antagonistic effects on P2 receptors. Of those, nine different plant sources demonstrated effects on P2X2, P2X3, P2X7, and possibly P2Y12 receptor subtypes. Microorganisms, which represent the largest group, with 26 different sources, showed effects on both receptor subtypes, ranging from P2X1 to P2X4 and P2X7, and P2Y1, P2Y2, P2Y4, and P2Y6. In addition, there were seventeen animal sources that affected P2X7 and P2Y1 and P2Y12 receptors. Natural products have provided some fascinating new mechanisms and sources to better understand the P2 receptor antagonism. Moreover, current investigations should clarify further pharmacological mechanisms in order to consider these products as potential new medicines.

Abstract: In order to understand the antifungal activity of some derivatives of sanguinarine (S) and chelerythrine (C) and their structure-activity relationships, sixteen derivatives of S and C were prepared and evaluated for in vitro antifungal activity against seven phytopathogenic fungi by the mycelial growth rate method. The results showed that S, C and their 6-alkoxy dihydro derivatives S₁–S₄, C₁–C₄ and 6-cyanodihydro derivatives S₅, C₅ showed significant antifungal activity at 100 µg/mL against all the tested fungi. For most tested fungi, the median effective concentrations of S, S₁, C and C₁ were in a range of 14–50 µg/mL. The structure-activity relationship showed that the C=N⁺ moiety was the determinant for the antifungal activity of S and C. S₁–S₅ and C₁–C₅ could be considered as the precursors of S and C, respectively. Thus, the present results strongly suggested that S and C or their derivatives S₁–S₅ and C₁–C₅ should be considered as good lead compounds or model molecules to develop new anti-phytopathogenic fungal agents.

Abstract: The substitution of a hydroxyl group by a fluorine atom in a potential drug is an efficient reaction that can, in principle, improve its pharmacological properties. Herein, the synthesis of the novel compound 5′-fluoro-5′-deoxyacadesine (5′-F-AICAR), a strict analogue of AICAR that cannot be 5′-phosphorylated to ZMP by cellular kinases, is reported.

Abstract: Sol-gel entrapment is an efficient immobilization technique that allows preparation of robust and highly stable biocatalysts. Lipase from Candida antarctica B was immobilized by sol-gel entrapment and by sol-gel entrapment combined with adsorption on Celite 545, using a ternary silane precursor system. After optimization of the immobilization protocol, the best enzyme loading was 17.4 mg/g support for sol-gel entrapped lipase and 10.7 mg/g support for samples obtained by entrapment and adsorption. Sol-gel immobilized enzymes showed excellent values of enantiomeric ratio E and activity when ionic liquid 1-octyl-3-methyl-imidazolium tetrafluoroborate was used as additive. Immobilization increased the stability of the obtained biocatalysts in several organic solvents. Excellent operational stability was obtained for the immobilized lipase, maintaining unaltered catalytic activity and enantioselectivity during 15 reuse cycles. The biocatalysts were characterized using scanning electron microscopy (SEM) and fluorescence microscopy. The improved catalytic efficiency of entrapped lipases recommends their application for large-scale kinetic resolution of optically active secondary alcohols.

Abstract: The replacement of hazardous solvents and the utilization of catalytic processes are two key points of the green chemistry movement, so aqueous organometallic catalytic processes are of great interest in this context. Nevertheless, these processes require not only the use of water-soluble ligands such as phosphanes to solubilise the transition metals in water, but also the use of mass transfer agents to increase the solubility of organic substrates in water. In this context, phosphanes based on a cyclodextrin skeleton are an interesting alternative since these compounds can simultaneously act as mass transfer agents and as coordinating species towards transition metals. For twenty years, various cyclodextrin-functionalized phosphanes have been described in the literature. Nevertheless, while their coordinating properties towards transition metals and their catalytic properties were fully detailed, their mass transfer agent properties were much less discussed. As these mass transfer agent properties are directly linked to the availability of the cyclodextrin cavity, the aim of this review is to demonstrate that the nature of the reaction solvent and the nature of the linker between cyclodextrin and phosphorous moieties can deeply influence the recognition properties. In addition, the impact on the catalytic activity will be also discussed.

Abstract: Traditionally, isotope-labelled DNA and RNA have been fundamental to nucleic acid structural studies by NMR. Four-stranded nucleic acid architectures studies increasingly benefit from a plethora of nucleotide conjugates for resonance assignments, the identification of hydrogen bond alignments, and improving the population of preferred species within equilibria. In this paper, we review their use for these purposes. Most importantly we identify reasons for the failure of some modifications to result in quadruplex formation.

Abstract: Locked nucleic acids (LNA) confer high thermal stability and nuclease resistance to oligonucleotides. The discovery of polymerases that accept LNA triphosphates has led us to propose a scheme for the amplification and re-generation of LNA-containing oligonucleotide libraries. Such libraries could be used for in vitro selection of e.g., native LNA aptamers. We maintained an oligonucleotide library encoding 40 randomized positions with LNA ATP, GTP, CTP, and TTP for 7 rounds of ‘mock’ in vitro selection in the absence of a target and analyzed the sequence composition after rounds 1, 4 and 7. We observed a decrease in LNA-A content from 20.5% in round 1 to 6.6% in round 7. This decrease was accompanied by a substantial bias against successive LNA-As (poly-LNA adenosine tracts) and a relative over-representation of single LNA-As. Maintaining a library with LNA TTP yielded similar results. Together, these results suggest that dispersed LNA monomers are tolerated in our in vitro selection protocol, and that LNA-modified libraries can be sustained for up to at least seven selection rounds, albeit at reduced levels. This enables the discovery of native LNA aptamers and similar oligonucleotide structures.

Abstract: The many virtues that made the yeast Saccharomyces cerevisiae a dominant model organism for genetics and molecular biology, are now establishing its role in chemical genetics. Its experimental tractability (i.e., rapid doubling time, simple culture conditions) and the availability of powerful tools for drug-target identification, make yeast an ideal organism for high-throughput phenotypic screening. It may be especially applicable for the discovery of chemical probes targeting highly conserved cellular processes, such as metabolism and bioenergetics, because these probes would likely inhibit the same processes in higher eukaryotes (including man). Importantly, changes in normal cellular metabolism are associated with a variety of diseased states (including neurological disorders and cancer), and exploiting these changes for therapeutic purposes has accordingly gained considerable attention. Here, we review progress and challenges associated with forward chemical genetic screening in yeast. We also discuss evidence supporting these screens as a useful strategy for discovery of new chemical probes and new druggable targets related to cellular metabolism.

Abstract: Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs) in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenyl)benzamides 8–19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8–10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 μM. Compounds 11–15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B) assay against seven human cancer cell lines: HT-29 (colon), HCT-116 (colon), MDA-231 (breast), A549 (lung), Hep3B (hepatoma), HeLa (cervical) and Caki (kidney) and one normal cell line (HSF). Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC₅₀: 29.17 μM), human lung cancer (A549, IC₅₀: 32.09 μM) cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC₅₀: 35.49 μM and HCT 116, IC₅₀: 27.56 μM), human lung cancer (A549, IC₅₀: 30.69 μM), and human cervical cancer (HeLa, IC₅₀: 34.41 μM) cell lines. The apparent permeability coefficient (P_app, cm/s) values of two compounds (16 and 17) were evaluated as 68.21 and 71.48 × 10⁻⁶ cm/s by Caco-2 cell permeability assay.

Abstract: Ipomea hederacea Jacq. (kaladana or ivy leaf morning-glory), a member of the family Convolvulaceae, is used primarily for its seeds and recognized for its medicinal properties, especially in Asian countries. This medicinal herb contains various valuable chemical constituents such as ecdysteriods, steroidal glycosides, aromatic acids, triterpenes, amino acids, organic acids, mineral elements and vitamins. A number of pharmacological properties such as diuretic, anthelmintic, blood purifier, deobstruent, laxative, carminative and anti-inflammatory actions have been ascribed to this plant, besides its use to treat abdominal diseases, fevers, headache and bronchitis. This review focuses on compositional, medicinal and therapeutic properties of this plant, as a potential sources of bioactive molecules for medicinal and nutraceutical applications.

Abstract: Density-functional theory calculations are presented for low-energy La@C₇₂, La@C₇₄ and La@C₇₆ isomers with IPR (isolated pentagon rule) and non-IPR cages. The relative isomeric production yields at high temperatures are evaluated using the calculated terms, and the relationships to observations are discussed.

Abstract: The effect of ionic surfactants and manufacturing methods on the separation and distribution of multi-wall carbon nanotubes (CNTs) in a silicone matrix are investigated. The CNTs are dispersed in an aqueous solution of the anionic surfactant dodecylbenzene sulfonic acid (DBSA), the cationic surfactant cetyltrimethylammonium bromide (CTAB), and in a DBSA/CTAB surfactant mixture. Four types of CNT-based composites of various concentrations from 0 to 6 vol.% are prepared by simple mechanical mixing and sonication. The morphology, electrical and thermal conductivity of the CNT-based composites are analyzed. The incorporation of both neat and modified CNTs leads to an increase in electrical and thermal conductivity. The dependence of DC conductivity versus CNT concentration shows percolation behaviour with a percolation threshold of about 2 vol.% in composites with neat CNT. The modification of CNTs by DBSA increases the percolation threshold to 4 vol.% due to the isolation/separation of individual CNTs. This, in turn, results in a significant decrease in the complex permittivity of CNT–DBSA-based composites. In contrast to the percolation behaviour of DC conductivity, the concentration dependence of thermal conductivity exhibits a linear dependence, the thermal conductivity of composites with modified CNTs being lower than that of composites with neat CNTs. All these results provide evidence that the modification of CNTs by DBSA followed by sonication allows one to produce composites with high homogeneity.

Abstract: Three new γ-butenolide derivatives 1–3, named spiculisporic acids B–D, were isolated from the culture of Aspergillus sp. HDf2, a marine-derived fungus that resides in the sea urchin, Anthocidaris crassispina. The structures of 1–3 were elucidated on the basis of spectroscopic methods, including MS and 2D NMR techniques. Their in vitro cytotoxic activities against two cell lines (SGC-7901, human gastric adenocarcinoma and SPC-A-1, human lung adenocarcinoma) and inhibitory activities against Staphylococcus aureus ATCC 51650 were investigated.

Abstract: A series of twelve amides was synthesized via aminolysis of substituted pyrazinecarboxylic acid chlorides with substituted benzylamines. Compounds were characterized with analytical data and assayed in vitro for their antimycobacterial, antifungal, antibacterial and photosynthesis-inhibiting activity. 5-tert-Butyl-6-chloro-N-(4-methoxybenzyl)pyrazine-2-carboxamide (12) has shown the highest antimycobacterial activity against Mycobacterium tuberculosis (MIC = 6.25 µg/mL), as well as against other mycobacterial strains. The highest antifungal activity against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-chloro-N-(3-trifluoromethylbenzyl)-pyrazine-2-carboxamide (2, MIC = 15.62 µmol/L). None of the studied compounds exhibited any activity against the tested bacterial strains. Except for 5-tert-butyl-6-chloro-N-benzylpyrazine-2-carboxamide (9, IC₅₀ = 7.4 µmol/L) and 5-tert-butyl-6-chloro-N-(4-chlorobenzyl)pyrazine-2-carboxamide (11, IC₅₀ = 13.4 µmol/L), only moderate or weak photosynthesis-inhibiting activity in spinach chloroplasts (Spinacia oleracea L.) was detected.

Abstract: In this work, mesoporous shells were constructed on solid silica cores by employing anionic surfactante. A co-structure directing agent (CSDA) has assisted the electrostatic interaction between negatively charged silica particles and the negatively charged surfactant molecules. Synthetic parameters such as reaction time and temperature had a significant impact on the formation of mesoporous silica shelld and their textural properties such as surface area and pore volume. Core-mesoporous shell silica spheres were characterized by small angle X-ray scattering, transmission electron microscopy, and N₂ adsorption–desorption analysis. The synthesized particles have a uniformly mesoporous shell of 34–65 nm and possess a surface area of ca. 7–324 m²/g, and pore volume of ca. 0.008–0.261 cc/g. The core-mesoporous shell silica spheres were loaded with ketoprofen drug molecules. The in vitro drug release study suggested that core-mesoporous shell silica spheres are a suitable nanocarrier for drug molecules offering the possibility of having control over their release rate.

Abstract: DNA circuits have proven to be useful amplifiers for diagnostic applications, in part because of their modularity and programmability. In order to determine whether different circuits could be modularly stacked, we used a catalytic hairpin assembly (CHA) circuit to initiate a hybridization chain reaction (HCR) circuit. In response to an input nucleic acid sequence, the CHA reaction accumulates immobilized duplexes and HCR elongates these duplexes. With fluorescein as a reporter each of these processes yielded 10-fold signal amplification in a convenient 96-well format. The modular circuit connections also allowed the output reporter to be readily modified to a G-quadruplex-DNAzyme that yielded a fluorescent signal.

Abstract: The solubility, absorption and distribution of a drug are involved in the basic aspects of oral bioavailability Solubility is an essential characteristic and influences the efficiency of the drug. Over the last ten years, the number of poorly soluble drugs has steadily increased. One of the progressive ways for increasing oral bioavaibility is the technique of nanoparticle preparation, which allows many drugs to thus reach the intended site of action. Candesartan cilexetil and atorvastatin, belonging to class II of the biopharmaceutical classification system, were chosen as model active pharmaceutical ingredients in this study. Forty samples were prepared either by antisolvent precipitation/solvent evaporation method or by the emulsion/solvent evaporation technique with various commonly used surface-active excipients as nanoparticle stabilizers. All samples were analyzed by means of dynamic light scattering. The particle size of the determined 36 nanoparticle samples was to 574 nm, whereas 32 samples contained nanoparticles of less than 200 nm. Relationships between solvents and excipients used and their amount are discussed. Based on the results the investigated solvent evaporation methods can be used as an effective and an affordable technique for the preparation of nanoparticles.

Abstract: Recent developments in the synthesis of CuO nanoparticles (NPs) and their application to the [3+2] cycloaddition of azides with terminal alkynes are reviewed. With respect to the importance of click chemistry, CuO hollow NPs, CuO hollow NPs on acetylene black, water-soluble double-hydrophilic block copolymer (DHBC) nanoreactors and ZnO–CuO hybrid NPs were synthesized. Non-conventional energy sources such as microwaves and ultrasound were also applied to these click reactions, and good catalytic activity with high regioselectivity was observed. CuO hollow NPs on acetylene black can be recycled nine times without any loss of activity, and water-soluble DHBC nanoreactors have been developed for an environmentally friendly process.

Abstract: In Korean herbal medicine dandelion (Taraxacum officinale, TO) has been used to improve energy levels and health. However, the effects of TO in experimental models remain unclear. We examined the anti-fatigue and immune-enhancing effects of TO in mice by performing a forced swimming test (FST) and in vitro by using peritoneal macrophages, respectively. After daily oral administration of TO, blood biochemical parameters related to fatigue were measured after the FST. FST immobility time was significantly decreased in the TO-treated group (100 mg/kg) on the tenth day. TO (10 and 100 mg/kg) treatment significantly increased glucose levels, acting as an energy source. The level of lactic dehydrogenase, which is an accurate indicator of muscle damage, tended to decline after TO administration (10 and 100 mg/kg). When TO (100 mg/kg) was orally administered to mice, blood urea nitrogen levels decreased significantly. We also examined the effect of TO on the production of cytokines and nitric oxide (NO) in mouse peritoneal macrophages. When TO was used in combination with recombinant interferon-gamma (rIFN-γ), a noticeable cooperative induction of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-12p70, and IL-10 production was observed. Furthermore, in peritoneal macrophages, rIFN-γ plus TO treatment significantly increased the production of NO through inducible nitric oxide synthase (iNOS) induction. Taken together, these results suggest that TO improves fatigue-related indicators and immunological parameters in mice.

Abstract: Among the currently available positron emitters suitable for Positron Emission Tomography (PET), ¹²⁴I has the longest physical half-life (4.2 days). The long half-life and well-investigated behavior of iodine in vivo makes ¹²⁴I very attractive for pharmacological studies. In this communication, we describe a simple yet effective method for the synthesis of novel ¹²⁴I labeled compounds intended for PET imaging of arylsulfatase activity in vivo. Arylsulfatases have important biological functions, and genetic deficiencies of such functions require pharmacological replacement, the efficacy of which must be properly and non-invasively evaluated. These enzymes, even though their natural substrates are mostly of aliphatic nature, hydrolyze phenolic sulfates to phenol and sulfuric acid. The availability of [¹²⁴I]iodinated substrates is expected to provide a PET-based method for measuring their activity in vivo. The currently available methods of synthesis of iodinated arylsulfates usually require either introducing of a protected sulfate ester early in the synthesis or introduction of sulfate group at the end of synthesis in a separate step. The described method gives the desired product in one step from an aryl-alkyl cyclic sulfate. When treated with iodide, the source cyclic sulfate opens with substitution of iodide at the alkyl center and gives the desired arylsulfate monoester.

Abstract: The phenolic compound phloridzin (phloretin 2′-O-glucoside, variously named phlorizin, phlorrhizin, phlorhizin or phlorizoside) is a prominent member of the chemical class of dihydrochalcones, which are phenylpropanoids. Phloridzin is specifically found in apple and apple juice and known for its biological properties. In particular we were attracted by potential dermo-cosmetic applications. Here we report the synthesis, stability studies and antimicrobial activity of compound F2, a new semi-synthetic derivative of phloridzin. The new derivative was also included in finished formulations to evaluate its stability with a view to a potential topical use. Stability studies were performed by HPLC; PCL assay and ORAC tests were used to determine the antioxidant activity. F2 presented an antioxidant activity very close to that of the parent phloridzin, but, unlike the latter, was more stable in formulations. To further explore potential health claims, antifungal activity of phloridzin and its derivative F2 were determined; the results, however, were rather low; the highest value was 31,6% of inhibition reached by F2 on Microsporum canis at the highest dose.

Abstract: We report herein the synthesis and characterization of 9-(2-diallylaminoethyl) adenine. We evaluated two different synthetic routes starting with adenine where the optimal route was achieved through coupling of 9-(2-chloroethyl)adenine with diallylamine. The cyclopolymerization and cyclo-copolymerization of 9-(2-diallylaminoethyl)adenine hydrochloride salt resulted in low molecular weight oligomers in low yields. In contrast, 9-(2-diallylaminoethyl)adenine failed to cyclopolymerize, however, it formed a copolymer with SO₂ in relatively good yields. The molecular weights of the cyclopolymers were around 1,700–6,000 g/mol, as estimated by SEC. The cyclo-copolymer was stable up to 226 °C. To the best of our knowledge, this is the first example of a free-radical cyclo-copolymerization of a neutral alkyldiallylamine derivative with SO₂. These polymers represent a novel class of carbocyclic polynucleotides.

Abstract: Six silver(I) coordination complexes have been prepared and structurally characterised. Mixed chalcogen-donor acenaphthene ligands L1–L3 [Acenap(EPh)(E'Ph)] (Acenap = acenaphthene-5,6-diyl; E/E' = S, Se, Te) were independently treated with silver(I) salts (AgBF₄/AgOTf). In order to keep the number of variables to a minimum, all reactions were carried out using a 1:1 ratio of Ag/L and run in dichloromethane. The nature of the donor atoms, the coordinating ability of the respective counter-anion and the type of solvent used in recrystallisation, all affect the structural architecture of the final silver(I) complex, generating monomeric, silver(I) complexes {[AgBF₄(L)₂] (1 L = L1; 2 L = L2; 3 L = L3), [AgOTf(L)₃] (4 L = L1; 5 L = L3), [AgBF₄(L)₃] (2a L = L1; 3a L = L3)} and a 1D polymeric chain {[AgOTf(L3)]_n 6}. The organic acenaphthene ligands L1-L3 adopt a number of ligation modes (bis-monodentate μ₂-η²-bridging, quasi-chelating combining monodentate and η⁶-E(phenyl)-Ag(I) and classical monodentate coordination) with the central silver atom at the centre of a tetrahedral or trigonal planar coordination geometry in each case. The importance of weak interactions in the formation of metal-organic structures is also highlighted by the number of short non-covalent contacts present within each complex.

Abstract: An asymmetric Claisen rearrangement using Oppolzer’s camphorsultam was developed. Under thermal conditions, a geraniol-derived substrate underwent the rearrangement with good stereoselectivity. The absolute configuration of the newly formed all-carbon quaternary stereocenter was confirmed by the total synthesis of (+)-bakuchiol from the rearrangement product.

Abstract: Herbal Epimedium species have been widely in Traditional Chinese Medicine for sexual enhancement, immunity improvement, anticancer and anti-aging treatment, with flavonoids and polysaccharides being the major active components. However, exhaustive depletion of wild sources warrants germplasm evaluation and quality resource exploration. A preliminarily analysis had previously indicated that a specific local geographic accession of Epimedium sagittatum found in Luotian (LT) county of Hubei Province (China) had a much higher content of total flavonoids and polysaccharides. In this study, we further investigated the medicinal component variation in the LT type under different light intensities and in different regions by the common-garden experiment. The results indicated a light intensity range of 40–160 μmol/m²/s was the most suitable for the synthesis and accumulation of total flavonoids, while polysaccharide accumulation was negatively correlated with the light intensity. Icariin was the component displaying the highest content among flavonoids, and the content of major flavonoid bioactive components was relatively stable in the third year after cultivation. There was significant correlation between the major flavonol glycoside constituents and the geographic location, and Central China followed by Northern China were the highly suitable regions for cultivation of LT type E. sagittatum. The results revealed that there was a functional balance between flavonoids and polysaccharides at different developmental stages, and the best harvesting stage should consider the primary contents of interest. This study provides important information on the exploration of quality resources, further breeding approaches and cultivation practices of E. sagittatum, and thus the important insights to enhance our understanding of quality control of traditional medicinal plants.

Abstract: Renovascular hypertension has robust effects on control of blood pressure, including an impairment in baroreflex mechanisms, which involves oxidative stress. Although α-lipoic acid (LA) has been described as a potent antioxidant, its effect on renovascular hypertension and baroreflex sensitivity (BRS) has not been investigated. In the present study we analyzed the effects caused by chronic treatment with LA on blood pressure, heart rate and baroreflex sensitivity (sympathetic and parasympathetic components) in renovascular hypertensive rats. Male Wistar rats underwent 2-Kidney-1-Clip (2K1C) or sham surgery and were maintained untouched for four weeks to develop hypertension. Four weeks post-surgery, rats were treated with LA (60 mg/kg) or saline for 14 days orally. On the 15th day mean arterial pressure (MAP) and heart rate (HR) were recorded. In addition, baroreflex sensitivity test using phenylephrine (8 µg/kg, i.v.) and sodium nitroprusside (25 µg/kg, i.v.) was performed. Chronic treatment with LA decreased blood pressure in hypertensive animals; however, no significant changes in baseline HR were observed. Regarding baroreflex, LA treatment increased the sensitivity of both the sympathetic and parasympathetic components. All parameters studied were not affected by treatment with LA in normotensive animals. Our data suggest that chronic treatment with LA promotes antihypertensive effect and improves baroreflex sensitivity in rats with renovascular hypertension.

Abstract: One-pot synthesis of 2-phenylimidazo[1,2-α]pyridines from acetophenone, [Bmim]Br₃ and 2-aminopyridine under solvent-free conditions in the presence of Na₂CO₃, gave the corresponding 2-phenylimidazo[1,2-α]pyridines in excellent yields ranging from 72% to 89%.

Abstract: C-di-GMP, a cyclic guanine dinucleotide, has been shown to regulate biofilm formation as well as virulence gene expression in a variety of bacteria. Analogues of c-di-GMP have the potential to be used as chemical probes to study c-di-GMP signaling and could even become drug leads for the development of anti-biofilm compounds. Herein we report the synthesis and biophysical studies of a series of c-di-GMP analogues, which have both phosphate and sugar moieties simultaneously modified (called endo-S-c-di-GMP analogues). We used computational methods to predict the relative orientation of the guanine nucleobases in c-di-GMP and analogues. DOSY NMR of the endo-S-c-di-GMP series showed that the polymorphism of c-di-GMP can be tuned with conservative modifications to the phosphate and sugar moieties (conformational steering). Binding studies with Vc2 RNA (a class I c-di-GMP riboswitch) revealed that conservative modifications to the phosphate and 2'-positions of c-di-GMP dramatically affected binding to class I riboswitch.

Abstract: We have developed a set of DNA circuits that execute during gel electrophoresis to yield immobile, fluorescent features in the gel. The parallel execution of orthogonal circuits led to the simultaneous production of different fluorescent lines at different positions in the gel. The positions of the lines could be rationally manipulated by changing the mobilities of the reactants. The ability to program at the nanoscale so as to produce patterns at the macroscale is a step towards programmable, synthetic chemical systems for generating defined spatiotemporal patterns.

Abstract: Ischemic stroke is a devastating disease with a complex pathophysiology. Galangin is a natural flavonoid isolated from the rhizome of Alpina officinarum Hance, which has been widely used as an antioxidant agent. However, its effects against ischemic stroke have not been reported and its related neuroprotective mechanism has not really been explored. In this study, neurological behavior, cerebral infarct volumes and the improvement of the regional cortical blood flow (rCBF) were used to evaluate the therapeutic effect of galangin in rats impaired by middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia. Furthermore, the determination of mitochondrial function and Western blot of apoptosis-related proteins were performed to interpret the neuroprotective mechanism of galangin. The results showed that galangin alleviated the neurologic impairments, reduced cerebral infarct at 24 h after MCAO and exerted a protective effect on the mitochondria with decreased production of mitochondrial reactive oxygen species (ROS). These effects were consistent with improvements in the membrane potential level (Dym), membrane fluidity, and degree of mitochondrial swelling in a dose-dependent manner. Moreover, galangin significantly improved the reduced rCBF after MCAO. Western blot analysis revealed that galangin also inhibited apoptosis in a dose-dependent manner concomitant with the up-regulation of Bcl-2 expression, down-regulation of Bax expression and the Bax/Bcl-2 ratio, a reduction in cytochrome c release from the mitochondria to the cytosol, the reduced expression of activated caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP). All these data in this study demonstrated that galangin might have therapeutic potential for ischemic stroke and play its protective role through the improvement in rCBF, mitochondrial protection and inhibiting caspase-dependent mitochondrial cell death pathway for the first time.

Abstract: The present study was undertaken to test the hypothesis that NADPH oxidase-derived reactive oxygen species (ROS) are involved in isoliquiritigenin (ISL)-induced monocytic differentiation in human acute promyelocytic leukemia HL-60 cells. Morphological changes, cell surface markers CD11b/CD14 and NBT-reducing ability were used to determine the differentiation of HL-60 cells, and 2,7-dichlorofluorescein (DCFH-DA) was used to detect the level of intracellular ROS. ISL-induced HL-60 cell differentiation was accompanied by an increase in the intracellular ROS levels. l-Buthionine-(S,R)-sulfoximine (BSO), N-acetyl-l-cysteine (NAC), superoxide dismutase (SOD) and 4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl (Tempol) were used to interfere with ROS production. NADPH oxidase inhibitors, apocynin (APO) and diphenyleneiodonium (DPI) were used to study the role of NADPH oxidase in ISL-induced HL-60 cell differentiation. The ISL-induced HL-60 cell differentiation and intracellular ROS generation were enhanced by the oxidant BSO and inhibited by the antioxidants NAC, SOD, and tempol, and were also inhibited by the NADPH oxidase inhibitors APO and DPI. The protein and mRNA expression of the NADPH oxidase subunits gp91phox and p47phox were determined by Western blotting and RT-PCR, respectively. The levels of translation and transcription of the NADPH oxidase subunits gp91phox and p47phox increased markedly in a concentration-dependent manner. These findings suggest that NADPH oxidase plays a critical role in HL-60 cell differentiation induced by ISL and that NADPH oxidase-derived ROS is involved in the differentiation mechanism.

Abstract: Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical investigation mainly directed at the isolation of pentacyclic triterpenes. The compounds friedelin (1), β-friedelinol (2), 3-oxo-21β-H-hop-22(29)-ene (7), 3,4-seco-friedelan-3,11β-olide (8), 3β-hydroxy-21β-H-hop-22(29)-ene (9), 3,4-seco-21β-H-hop-22(29)-en-3-oic acid (10), 3,4-seco-friedelan-3-oic acid (11), and sitosterol were identified in the hexane extract of M. robusta leaves. Compounds 8 and 9 are described herein for the first time. The structure and stereochemistry of both compounds were experimentally established by IR, HRLC-MS, and 1D (¹H, ¹³C, and DEPT 135) and 2D (HSQC, HMBC and COSY) NMR data and supported by correlations with carbon chemical shifts calculated using the DFT method (BLYP/6-31G* level). Compounds 7 and 10 are also described for the first time, and their chemical structures were established by comparison with NMR data of similar structures described in the literature and correlations with BLYP/6-31G* calculated carbon chemical shifts. Compound 9, a mixture of 11 and sitosterol, and 3β,11β-dihydroxyfriedelane (4) were evaluated by the Ellman’s method and all these compounds showed acethylcholinesterase inhibitory properties.

Abstract: Rhizoma Atractylodes macrocephala (AM) has been used in Traditional Chinese Medicine (TCM) for about 2,000 years. In the study, we firstly determined the antioxidant levels of five AM extracts by •OH-scavenging, •O₂⁻-scavenging, Fe²⁺-chelating, Cu²⁺-chelating, DPPH·-scavenging, and ABTS⁺·-scavenging assays. After measurement of the chemical contents in five AM extracts, we quantitatively analyzed the correlations between antioxidant levels and chemical contents. It was observed that total phenolics and total flavonoids had significant positive correlations with antioxidant levels (R = 0.685 and 0.479, respectively). In contrast, total sugars and total saponins presented lower correlations with antioxidant levels (R = −0.272 and 0.244, respectively). It means that antioxidant activity of AM should be attributed to total phenolics (including phenolic acids and flavonoids), and not total sugars and total saponins. Further analysis indicated that phenolic acids exhibited higher R values with radical-scavenging assays (R = 0.32–1.00), while flavonoids showed higher R values with metal-chelating assays (R= 0.86 and 0.90). In conclusion, AM exerts its antioxidant effect through metal-chelating, and radical-scavenging which is via donating hydrogen atom and donating electron. Its metal-chelating may result from flavonoids, while its radical-scavenging can be attributed to phenolic acids, especially caffeic acid, ferulic acid, and protocatechuic acid.

Abstract: The Amaryllidaceae family is well known for its pharmacologically active alkaloids. An important approach to treat Alzheimer’s disease involves the inhibition of the enzyme acetylcholinesterase (AChE). Galanthamine, an Amaryllidaceae alkaloid, is an effective, selective, reversible, and competitive AchE inhibitor. This work was aimed at studying the alkaloid composition of four wild Argentinian Amarillydaceae species for the first time, as well as analyzing their inhibitory activity on acetylcholinesterase. Alkaloid content was characterized by means of GC-MS analysis. Chloroform basic extracts from Habranthus jamesonii, Phycella herbertiana, Rhodophiala mendocina and Zephyranthes filifolia collected in the Argentinian Andean region all contained galanthamine, and showed a strong AChE inhibitory activity (IC₅₀ between 1.2 and 2 µg/mL). To our knowledge, no previous reports on alkaloid profiles and AChEIs activity of wild Argentinian Amarillydaceae species have been publisihed. The demand for renewable sources of industrial products like galanthamine and the need to protect plant biodiversity creates an opportunity for Argentinian farmers to produce such crops.

Abstract: Two series of thiosemicarbazone-based iron chelators (twenty-seven compounds) were designed and synthesized using a microwave-assisted approach. Quinoline and halogenated phenyl were selected as parent scaffolds on the basis of a similarity search. The lipophilicity of the synthesized compounds was measured using HPLC and then calculated. Primary in vitro screening of the synthesized compounds was performed against eight pathogenic fungal strains. Only a few compounds showed moderate activity against fungi, and (E)-2-(quinolin-2-ylvinyl)-N,N-dimethylhydrazine-carbothioamide appeared to be more effective than fluconazole against most of the fungal strains tested. Antiproliferative activity was measured using a human colon cancer cell line (HCT-116). Several of the tested compounds showed submicromolar antiproliferative activity. Compounds were also tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The structure-activity relationships are discussed for all of the compounds.

Abstract: Toll-like receptors (TLRs) belong to a family of innate immune receptors that detect and clear invading microbial pathogens. Specifically intracellular TLRs such as TLR3, TLR7, TLR8 and TLR9 recognize nucleic acids such as double-stranded RNA, single-stranded RNA and CpG DNA respectively derived from microbial components. Upon infection, nucleic acid sensing TLRs signal within endosomal compartment triggering the induction of essential proinflammatory cytokines and type I interferons to initiate innate immune responses thereby leading to a critical role in the development of adaptive immune responses. Thus, stimulation of TLRs by nucleic acids is a promising area of research for the development of novel therapeutic strategies against pathogenic infection, allergies, malignant neoplasms and autoimmunity. This review summarizes the therapeutic applications of nucleic acids or nucleic acid analogues through the modulation of TLR signaling pathways.

Abstract: Pseudopeptides containing the phosphinate moiety (-P(O)(OH)CH₂-) have been studied extensively, mainly as transition state analogue inhibitors of metalloproteases. The key synthetic aspect of their chemistry is construction of phosphinic dipeptide derivatives bearing appropriate side-chain substituents. Typically, this synthesis involves a multistep preparation of two individual building blocks, which are combined in the final step. As this methodology does not allow simple variation of the side-chain structure, many efforts have been dedicated to the development of alternative approaches. Recent achievements in this field are summarized in this review. Improved methods for the formation of the phosphinic peptide backbone, including stereoselective and multicomponent reactions, are presented. Parallel modifications leading to the structurally diversified substituents are also described. Finally, selected examples of the biomedical applications of the title compounds are given.

Abstract: Nucleoside triphosphates are moldable entities that can easily be functionalized at various locations. The enzymatic polymerization of these modified triphosphate analogues represents a versatile platform for the facile and mild generation of (highly) functionalized nucleic acids. Numerous modified triphosphates have been utilized in a broad palette of applications spanning from DNA-tagging and -labeling to the generation of catalytic nucleic acids. This review will focus on the recent progress made in the synthesis of modified nucleoside triphosphates as well as on the understanding of the mechanisms underlying their polymerase acceptance. In addition, the usefulness of chemically altered dNTPs in SELEX and related methods of in vitro selection will be highlighted, with a particular emphasis on the generation of modified DNA enzymes (DNAzymes) and DNA-based aptamers.

Abstract: Heart rate (HR) is a precisely regulated variable, which plays a critical role in health and disease. Elevated resting HR is a significant predictor of all-cause and cardiovascular mortality in the general population and patients with cardiovascular disease (CVD). β-blocking drugs exert negative effects on regional myocardial blood flow and function when HR reduction is eliminated by atrial pacing; calcium channel antagonists (CCAs) functionally antagonize coronary vasoconstriction mediated through α-adreno-receptors and are thus devoid of this undesired effect, but the compounds are nevertheless negative inotropes. From these observations derives the necessity to find alternative, more selective drugs to reduce HR through inhibition of specific electrical current (I_f). Ivabradine (IVA) is a novel specific HR-lowering agent that acts in sinus atrial node (SAN) cells by selectively inhibiting the pacemaker I_f current in a dose-dependent manner by slowing the diastolic depolarization slope of SAN cells, and by reducing HR at rest during exercise in humans. Coronary artery diseases (CAD) represent the most common cause of death in middle–aged and older adults in European Countries. Most ischemic episodes are triggered by an increase in HR, that induces an imbalance between myocardial oxygen delivery and consumption. IVA, a selective and specific inhibitor of the I_f current which reduced HR without adverse hemodynamic effects, has clearly and unequivocally demonstrated its efficacy in the treatment of chronic stable angina pectoris (CSAP) and myocardial ischemia with optimal tolerability profile due to selective interaction with I_f channels. The aim of this review is to point out the usefulness of IVA in the treatment of ischemic heart disease.

Abstract: Dendrimers are multifunctional, hyperbranched and perfectly defined macromolecules, synthesized layer after layer in an iterative manner. Besides the nature of the terminal groups responsible for most of the properties, the nature of the internal structure, and more precisely of the branching points, is also of crucial importance. For more than 15 years, we have demonstrated that the presence of phosphorus atom(s) at each branching point of the dendrimeric structure is particularly important and highly valuable for three main reasons: (i) the versatility of phosphorus chemistry that allows diversified organochemistry for the synthesis of dendrimers; (ii) the use of ³¹P-NMR, which is a highly valuable tool for the characterization of dendrimers; (iii) some properties (in the fields of catalysis, materials, and especially biology), that are directly connected to the nature of the internal structure and of the branching points. This review will give an overview of the methods of synthesis of phosphorus-containing dendrimers, as well on the ways to graft phosphorus derivatives as terminal groups, with emphasis on the various roles played by the chemistry of phosphorus.

Abstract: Bacteria can produce some compounds in response to their environment. These compounds are widely used in cosmetic and pharmaceutical applications. Some probiotics have immunomodulatory activities and modulate the symptoms of several diseases. Autoimmune diseases represent a complex group of conditions that are thought to be mediated through the development of autoreactive immunoresponses. Inflammatory bowel disease (IBD) is common autoimmune disease that affects many individuals worldwide. Previously, we found that the extracts of Rhodobacter sphaeroides (Lycogen) inhibited nitric oxide production and inducible nitric-oxide synthase expression in activated macrophages. In this study, the effect of Lycogen™, a potent anti-inflammatory agent, was evaluated in mice with dextran sodium sulfate (DSS)-induced colitis. Oral administration of Lycogen™ reduced the expressions of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in female BABL/c mice. In addition, the increased number of bacterial flora in the colon induced by DSS was amelirated by Lycogen™. The histological score of intestinal inflammation in 5% DSS-treated mice after oral administration of Lycogen™ was lower than that of control mice. Meanwhile, Lycogen™ dramatically prolonged the survival of mice with severe colitis. These findings identified that Lycogen™ is an anti-inflammatory agent with the capacity to ameliorate DSS-induced colitis.

Abstract: The 80% ethanol extract of Alstonia yunnanensis afforded five new monoterpenoid indole alkaloids: 11-hydroxy-6,7-epoxy-8-oxo-vincadifformine (1), 14-chloro-15-hydroxy- vincadifformine (2), perakine N₄-oxide (3), raucaffrinoline N₄-oxide (4), and vinorine N₁,N₄-dioxide (5), together with three known compounds: 11-methoxy-6,7-epoxy-8-oxo- vincadifformine (6), vinorine N₄-oxide (7) and vinorine (8). The structures of the isolated compounds were established based on 1D and 2D (¹H-¹H-COSY, HMQC, HMBC, and ROESY) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic potential against seven tumor cell lines and anti-inflammatory activities. Compounds 3, 4 and 7 exhibited weak cytotoxicity against the tested cell lines and selective inhibition of Cox-2 (>85%).

Abstract: A series of pyridines, pyrimidinones, oxazinones and their derivatives were synthesized as antimicrobial agents using citrazinic acid (2,6-dihydroxyisonicotinic acid) as a starting material. α,β-Unsaturated ketones 3a–c were condensed with cyanothio-acetamide in the presence of ammonium acetate to give 2-cyanopyridinethiones 4a–c, which were reacted with ethyl chloroacetate to yield the corresponding cyano esters 5a–c. The esters 5a–c were cyclized by action of sodium methoxide to aminoesters 6a–c, which were aminolyzed with ammonia to corresponding aminoamide derivatives 7a-c. Also, the esters 6a–c were hydrolyzed with NaOH to the corresponding sodium salt 8a–c, which were treated with acetic anhydride to afford 2-methyloxazinones 9a–c. The latter compounds were treated with ammonium acetate to afford 2-methylpyrimidinones 10a–c, followed by methylation with methyl iodide to yield 2,3-dimethyl-pyrimidinones 11a–c. The antimicrobial screening showed that many of these compounds have good antibacterial and antifungal activities comparable to streptomycin and fusidic acid used as reference drugs.

Abstract: Phenolic acid derivatives are typical constituents of Clerodendranthus spicatus which were considered to the active principles of this medicinal plant. These chemical constituents with their interesting frameworks and biological significance attracted our attention. As part of our ongoing chemical investigation of C. spicatus using various column chromatography techniques, a new phenolic compound, named clerodendranoic acid (1), was isolated from the aerial parts of C. spicatus together with five known ones, including rosmarinic acid (2), methyl rosmarinate (3), caffeic acid (4), methyl caffeate (5), ethyl caffeate (6). Their structures, including stereochemical configurations, were completely established by extensive spectroscopic methods, mainly inclvolving 1D, 2D NMR, as well as HRESIMS.

Abstract: Upon treatment with phenyl dichlorophosphate (PhOP=OCl₂) in acetonitrile at ambient temperature, a variety of ketoximes underwent a Beckmann rearrangement in an effective manner to afford the corresponding amides in moderate to high yields.

Abstract: Phytochemical investigations on the stem bark and roots of the tropical shrub Clausena anisata led to the isolation and characterization three carbazole alkaloids: girinimbine, murrayamine-A and ekeberginine; two peptide derivatives: aurantiamide acetate and N-benzoyl-l-phenylalaninyl-N-benzoyl-l-phenylalaninate; and a mixture of two phytosterols: sitosterol and stigmasterol. The structures of these compounds were established by nuclear magnetic resonance (¹H-NMR, ¹³C-NMR, COSY, HSQC, HMQC, HMBC and NOESY) spectroscopy and electrospray ionization mass spectrometry (MS).

Abstract: The mechanism of the intramolecular Diels–Alder (IMDA) reaction of benzoquinone 1, in the absence and in the presence of three water molecules, 1w, has been studied by means of density functional theory (DFT) methods, using the M05-2X and B3LYP functionals for exploration of the potential energy surface (PES). The energy and geometrical results obtained are complemented with a population analysis using the NBO method, and an analysis based on the global, local and group electrophilicity and nucleophilicity indices. Both implicit and explicit solvation emphasize the increase of the polarity of the reaction and the reduction of activation free energies associated with the transition states (TSs) of this IMDA process. These results are reinforced by the analysis of the reactivity indices derived from the conceptual DFT, which show that the increase of the electrophilicity of the quinone framework by the hydrogen-bond formation correctly explains the high polar character of this intramolecular process. Large polarization at the TSs promoted by hydrogen-bonds and implicit solvation by water together with a high electrophilicity-nucleophilicity difference consistently explains the catalytic effects of water molecules.