Evaluation of the Antiviral Activity of Tabamide A and Its Structural Derivatives against Influenza Virus.

Influenza viruses cause severe endemic respiratory infections in both humans and animals worldwide. The emergence of drug-resistant viral strains requires the development of new influenza therapeutics. Tabamide A (TA0), a phenolic compound isolated from tobacco leaves, is known to have antiviral activity. We investigated whether synthetic TA0 and its derivatives exhibit anti-influenza virus activity. Analysis of structure-activity relationship revealed that two hydroxyl groups and a double bond between C7 and C8 in TA0 are crucial for maintaining its antiviral action. Among its derivatives, TA25 showed seven-fold higher activity than TA0. Administration of TA0 or TA25 effectively increased survival rate and reduced weight loss of virus-infected mice. TA25 appears to act early in the viral infection cycle by inhibiting viral mRNA synthesis on the template-negative strand. Thus, the anti-influenza virus activity of TA0 can be expanded by application of its synthetic derivatives, which may aid in the development of novel antiviral therapeutics.

Design and Synthesis of π-Extended Resveratrol Analogues and In Vitro Antioxidant and Anti-Inflammatory Activity Evaluation.

The research on resveratrol (1) has been conducted intensively over a long time due to its proven antioxidant activity and disease-fighting capabilities. Many efforts have also been made to increase these biological effects. In the present study, six new extended aromatic resveratrol analogues containing naphthalene (2) and its bioisosteres quinoline (3 and 4), isoquinoline (5) quinoxaline (6) and quinazoline (7) scaffolds were designed and synthesized using an annulation strategy. The antioxidant and anti-inflammatory activities of these compounds were investigated. All compounds showed better antioxidant activity than resveratrol in ABTS assay. As for the anti-inflammatory test, 5 and 7 exhibited better activity than resveratrol. It is worth noting that nitrogen substitution on the extended aromatic resveratrol analogues has a significant impact on cell viability. Taking the antioxidant activities and NO inhibition activities into consideration, we conclude that isoquinoline analogue 5 may qualify for the further investigation of antioxidant and anti-inflammatory therapy. Furthermore, our study results suggest that in order to improve the biological activity of polyphenolic compounds, extended aromaticity and nitrogen substitution strategy could be a viable method for the design of future drug candidates.

Synthesis and in vitro evaluation of homoisoflavonoids as potent inhibitors of nitric oxide production in RAW-264.7 cells.

Syntheses of natural homoisoflavonoids, (±)-portulacanones A-C (4, 8 and 9), portulacanone D (6), isolated from Portulaca oleracea L. (POL) and their derivatives (3, 5 and 7) have been achieved for the first time along with the synthesis of known derivatives (1 and 2) and their in vitro inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages was evaluated as an indicator of anti-inflammatory activity. All the compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without obvious cytotoxicity. Compounds 3 (97.2% at 10 µM; IC50 = 1.26 µM) followed by 6 (portulacanone D) (92.5% at 10 µM; IC50 = 2.09 µM), 1 (91.4% at 10 µM; IC50 = 1.75 µM) and 7 (83.0% at 10 µM; IC50 = 2.91 µM) were the most potent from the series. This finding was further correlated with the suppressed expression of iNOS induced by LPS. Our promising preliminary results may provide the basis for the assessment of compound 3 as a lead structure for a NO production-targeted anti-inflammatory drug development and also could support the usefulness of POL as a folklore medicinal plant in the treatment of inflammatory diseases.

Enantioselective synthesis and antioxidant activity of 3,4,5-substituted piperidine derivatives.

In this study, 3,4,5-trisubstituted piperidines were synthesized enantioselectively, and their antioxidant activity was evaluated. The 3,4,5-trisubstituted piperidines containing TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and a spatially proximal hydroxy group showed good antioxidant activity. Some of these compounds showed IC50 values in a nanomolar range, comparable to that of TEMPO. Probably the TEMPO generated from the homolysis of the CON bond of 3,4,5-trisubstituted piperidines functions as a radical-scavenging entity, and the hydroxy group of piperidines has a synergistic effect to the antioxidant activity.

The potato rhizosphere microbiota correlated to the yield of three different regions in Korea.

We examined potato rhizosphere bacterial and fungal communities across three regions: Cheongju, Pyeongchang, and Gangneung. These regions have varying soil and climate conditions, resulting in different yields. We found that precipitation was the main limiting factor in our study while soil physiochemical factors affect bacterial and fungal microbiota in correlation with yield. Both bacterial and fungal microbiota showed distinct patterns according to the regions. ASVs positively correlated with yield were predominantly found in the Pyeongchang region which also produced the highest yields, while ASVs negatively correlated with yield were associated with Gangneung where the lowest yields were observed. The greatest bacterial and fungal diversity was detected in Pyeongchang consisting of Propionibacteriales, Burkholderiales, and Vicinamibacteriales. Gangneung, on the other hand primarily belong to Sordariales, Mortierellales, Cystofilobasidiales, and Tremellales. The putative yield-negative ASVs detected in Gangneung may have been influenced by drought stress. This work has highlighted key bacterial and fungal taxa as well as core taxa that may potentially be associated with high and low yields of potato in relation to metadata which includes soil chemical and physical parameters as well as weather data. Taken together we suggest that this information can be used to assess site suitability for potato production.

Ice-templated synthesis of tungsten oxide nanosheets and their application in arsenite oxidation.

Tungsten oxide (WO3) nanosheets were prepared as catalysts to activate hydrogen peroxide (H2O2) in arsenite (As(III)) oxidation. Ice particles were employed as templates to synthesize the WO3 nanosheets, enabling easy template removal via melting. Transmission electron microscopy and atomic force microscopy revealed that the obtained WO3 nanosheets were plate-like, with lateral sizes ranging from dozens of nanometers to hundreds of nanometers and thicknesses of <10 nm. Compared to that of the WO3 nanoparticle/H2O2 system, a higher efficiency of As(III) oxidation was observed in the WO3 nanosheet/H2O2 system. Electron spin resonance spectroscopy, radical quenching studies, and As(III) oxidation experiments under anoxic conditions suggested that the hydroperoxyl radical (HO2●) acted as the primary oxidant. The WO3 nanosheets possessed numerous surface hydroxyl groups and electrophilic metal centers, enhancing the production of HO2● via H2O2 activation. Various anions commonly present in As(III)-contaminated water exhibited little effect on As(III) oxidation in the WO3 nanosheet/H2O2 system. The high oxidation efficiency was maintained by adding H2O2 when it was depleted, suggesting that the catalytic activity of the WO3 nanosheets did not deteriorate after multiple catalytic cycles.

Antinociceptive activity of the Caesalpinia eriostachys Benth. ethanolic extract, fractions, and isolated compounds in mice.

Caesalpinia eriostachys Benth. (CE) is native to the Mexico and multiple effects have been observed from several plants belonging to the same family. CE was subjected to extraction with 95% ethanol, and the components were isolated through column chromatography. The structure of the compound was elucidated based on nuclear magnetic resonance (NMR) spectral data, electron ionization-mass (EI-MS) spectroscopy, and liquid chromatography-mass (LC-MS) spectroscopy. In vivo antinociceptive studies were conducted using writhing, 5% formalin, tail-flick, hot-plate, and von Frey filament tests. The ethanolic extract showed a significant effect in the acetic acid-induced pain model and nociceptive behavior in the formalin model (second phase). In hot-plate test and tail-flick test, the results showed no difference compared to the control group. The results suggest that the ethanolic extract may act peripherally to reduce pain. In the streptozotocin (STZ)-induced pain model, the ethanolic extract showed significant effect in the von Frey test model. The n-Hex (Hexane) and MC (Methylene chloride) fractions and isolated compounds, ellagic acid and agathisflavone, showed increased effect. Based on these results, we confirmed that the CE ethanolic extract and their compounds, ellagic acid and agathisflavone, have antinociceptive effect on diabetes mellitus-induced pain. Furthermore, the results of this study might be valuable for identifying compounds with antinociceptive activity from natural products.

Unconventional Kondo effect in redox active single organic macrocyclic transistors.

Cyclo[6]- and cyclo[8]pyrrole, two aromatic expanded porphyrins, were studied in a single-molecule transistor (SMT) setup. The analyses of these compounds allowed us to observe an uncommon absence of an even-odd effect in the Kondo resonance in discrete, metal-free organic macrocyclic compounds. The findings from the SMT measurements of these cyclopyrroles were in accord with those from cyclic voltammetry (CV) studies and theoretical analyses. These findings provide support for the notion that SMT measurements could be useful as a tool for the characterization of similar types of aromatic macrocyclic compounds.

Design, syntheses, and evaluation of Taspase1 inhibitors.

Taspase1 is a threonine protease responsible for cleaving MLL (Mixed-Lineage Leukemia) to achieve proper HOX gene expression. Subsequent studies identified additional Taspase1 substrates including Transcription Factor IIA (TFIIA) and Drosophila HCF. Taspase1 is essential for cell proliferation and is overexpressed in many cancer cell lines. Currently no small molecule inhibitors of this enzyme have been described. Here, we report the synthesis and evaluation of vinyl sulfone, vinyl ketone, epoxy ketone, and boronic acid inhibitors designed based on the preferred Taspase1 cleavage site (Ac-Ile-Ser-Gln-Leu-Asp). Specifically, we evaluated compounds in which the reactive warhead is positioned in place of the P1 aspartic acid side chain as well as at the C-terminus of the peptide. Interestingly, both classes of inhibitors were effective and vinyl ketones and vinyl sulfones showed the greatest potency for the target protease. These results suggest that Taspase1 has unique substrate recognition properties that could potentially be exploited in the design of potent and selective inhibitors of this enzyme.

Photocatalytic oxidation of urea on TiO2 in water and urine: mechanism, product distribution, and effect of surface platinization.

The photocatalytic oxidation of urea on TiO2 in water was compared with that in urine. Despite the presence of other organic compounds in urine, the oxidation efficiency of urea on TiO2 in urine was higher than that in water. This enhanced oxidation of urea in urine is ascribed to the higher production of •OH (primary oxidant for urea degradation) by the adsorption of PO43- (one constituent of urine) on the TiO2 surface. Among the various anions in urine, only PO43- was adsorbed on the surface of TiO2. Both the production of •OH and the oxidation of urea were enhanced in the presence of PO43-. These results indicate that the enhanced •OH production by in situ surface phosphorylation is the reason for the increased oxidation of urea in urine. Surface platinization of TiO2 enhanced the oxidation of urea in water. However, the oxidation efficiency of urea on Pt/TiO2 in urine was lower than that in water. This behavior is due to the adsorption of PO43- and SO42- in urine on Pt deposits, which inhibits the adsorption of oxygen and the interfacial electron transfer to oxygen. The product distribution (i.e., the molar ratio of NO3- to NH4+) in water was different from that in urine because the negatively charged surface of TiO2 in urine attracts the positively charged area of carbamic acid (intermediate) and encourages its decomposition into NH4+ and not into NO3-.

External Morphological Development of Post-larvae and Juveniles of Red Seabream, Pagrus major.

On the 15 days after hatching, the larvae was 4.24-5.10 mm (mean 4.66±2.18 mm) in total length, and the fins of the membrane started to develop into a fan shape and the melanophore was deposited upper the alimentary canal of the abdomen and on the bladder. At 35 days after hatching, the post-larvae formed a branch-shaped melanophore on the head part with a total length of 6.98-12.5 (mean 9.35±1.71) mm, formed on the upper and lower parts of the caudal part, formed on the upper and lower parts of the caudal part, and deposited under the head part and abdomen. At 40 days after hatching, the juvenile was 11.3-18.1 (mean 14.9±1.53) mm in total length.

Antinociceptive effect of N-(9,13b-dihydro-1H-dibenzo[c, f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide on different pain models in mice

Abstract N-(9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide (DDIAHB) is a new drug developed through molecular modelling and rational drug design by the molecular association of epinastine and salicylic acid. The present study was designed to assess the possible antinociceptive effects of DDIAHB on different pain models in male ICR mice. DDIAHB exerted the reductions of writhing numbers and pain behavior observed during the second phase in the formalin test in a dose-dependent manner. Moreover, DDIAHB increased the latency in the hot-plate test in a dose-dependent manner. Furthermore, intragastric administration DDIAHB caused reversals of decreased pain threshold observed in both streptozotocin-induced diabetic neuropathy and vincristine-induced peripheral neuropathy models. Additionally, intragastric pretreatment with DDIAHB also caused reversal of decreased pain threshold observed in monosodium urate-induced pain model. We also characterized the possible signaling molecular mechanism of the antinociceptive effect-induced by DDIAHB in the formalin model. DDIAHB caused reductions of spinal iNOS, p-STAT3, p-ERK and p-P38 levels induced by formalin injection. Our results suggest that DDIAHB shows an antinociceptive property in various pain models. Moreover, the antinociceptive effect of DDIAHB appear to be mediated by the reductions of the expression of iNOS, p-STAT3, p-ERK and p-P38 levels in the spinal cord in the formalin-induced pain model.

Evaluation of γ-oryzanol content and composition from the grains of pigmented rice-germplasms by LC-DAD-ESI/MS.

BACKGROUND: Rice is the staple food and one of the world's three major grain crops. Rice contains more than 100 bioactive substances including phytic acid, isovitexin, γ-oryzanol, phytosterols, octacosanol, squalene, γ-aminobutyric acid (GABA), tocopherol, tocotrienol derivatives, etc. Out of them, γ-oryzanol is known to have important biological profile such as anti-oxidants, inhibitor of cholesterol oxidation, reduce serum cholesterol levels in animals, effective in the treatment of inflammatory diseases, inhibit tumor growth, reduce blood pressure and promotes food storage stability when used as a food additive, etc. Hence in the present investigation, we aimed to evaluate the content and composition of γ-oryzanol from pigmented rice germplasms using a liquid chromatography with diode array detection and electrospray ionization-mass spectrometry (LC-DAD-ESI/MS). FINDINGS: In the present study, 33 exotic pigmented rice accessions (red, white and purple) have been evaluated. Among them, the contents of γ-oryzanol varied from 3.5 to 21.0 mg/100 g with a mean of 11.2 mg/100 g. A total of ten components of γ-oryzanol including Δ7-stigmastenyl ferulate were identified of which, cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, campesteryl ferulate and sitosteryl ferulate were identified as the major components. The mean proportions of steryl ferulates were in the descending order of 24-methylenecycloartanyl ferulate > cycloartenyl ferulate > campesteryl ferulate > sitosteryl ferulate > Δ7-campestenyl ferulate > campestanyl ferulate > sitostanyl ferulate > Δ7-stigmastenyl ferulate > stigamsteryl ferulate > Δ7-sitostenyl ferulate. Almost 11 accessions (33%) showed higher content than the control rice Chucheongbyeo and higher proportions ranged from 10 to 15 mg/100 g. Interestingly, the red rice accession Liberian Coll. B11/B-11 (21.0 mg/100 g) showed higher content γ-oryzanol than control rice Jeokjinjubyeo (19.1 mg/100 g) and the purple rice accession Padi Adong Dumarat, Mardi No.4376 (20.3 mg/100 g) showed a similar content with control rice Heugjinjubyeo (21.4 mg/100 g). CONCLUSIONS: Most of analyzed rice accessions were found to possess higher contents of γ-oryzanol than the control rice, Chucheongbyeo. In particular, the red accessions showed highest content than the white and purpleaccessions. The content and composition of γ-oryzanol in 33 exotic pigmented rice accessions have been evaluated and compared significantly by the present investigation.

High-order tunneling processes in single-porphyrin transistors.

Cotunneling and the Kondo effect are observed in single-electron transistors incorporating cobalt-porphyrins. These effects are attributed to high-order tunneling and strong coupling between the electrodes and the intervening porphyrin.

Validation of the proteasome as a therapeutic target in Plasmodium using an epoxyketone inhibitor with parasite-specific toxicity.

The Plasmodium proteasome has been suggested to be a potential antimalarial drug target; however, toxicity of inhibitors has prevented validation of this enzyme in vivo. We report a screen of a library of 670 analogs of the recent US Food and Drug Administration-approved inhibitor, carfilzomib, to identify compounds that selectively kill parasites. We identified one compound, PR3, that has significant parasite killing activity in vitro but dramatically reduced toxicity in host cells. We found that this parasite-specific toxicity is not due to selective targeting of the Plasmodium proteasome over the host proteasome, but instead is due to a lack of activity against one of the human proteasome subunits. Subsequently, we used PR3 to significantly reduce parasite load in Plasmodium berghei infected mice without host toxicity, thus validating the proteasome as a viable antimalarial drug target.

Immobilization of a hexaphyrin(1.0.1.0.0.0) derivative onto a tentagel-amino resin and its use in uranyl cation detection.

The synthesis of an isoamethyrin derivative containing two CH(2)CH(2)CO(2)CH(3) moieties in the beta-pyrrolic positions and its use in the colorimetric detection of the uranyl cation after immobilization onto a solid support is reported.

Redox behavior of cyclo[6]pyrrole in the formation of a uranyl complex.

A uranyl complex, the first metal complex to be formed from the cyclo[n]pyrrole series of expanded porphyrins, is formed when cyclo[6]pyrrole is treated with the uranyl cation under aerobic conditions. Spectroscopic, spectroelectrochemical, and electron spin resonance data of this species are consistent with the ligand in the complex being oxidized to an antiaromatic form.

Cyclo[n]pyrroles: size and site-specific binding to G-quadruplexes.

Inhibiting the enzyme telomerase by stabilizing the G-quadruplex has potential in anticancer drug design. Diprotonated cyclo[n]pyrroles represent a set of expanded porphyrin analogues with structures similar to that of telomestatin, a natural product known to bind to and stabilize G-quadruplexes. As a first step toward testing whether cyclo[n]pyrroles display a similar function, a series of diprotonated cyclo[n]pyrroles (where n = 6, 7, and 8) was each added to the human telomere repeat sequence d(T(2)AG(3))(4) and examined with mass spectrometry, ion mobility, and molecular dynamics calculations. Nano-ESI-MS indicated that the smaller the cyclo[n]pyrrole, the more strongly it binds to the telomeric sequence. It was also found that cyclo[6]pyrrole bound to d(T(2)AG(3))(4) better than octaethylporphyrin, a finding rationalized by cyclo[6]pyrrole having a 2+ charge, while octaethylporphyrin bears no charge. Ion mobility measurements were used to measure the collision cross section of each d(T(2)AG(3))(4)/cyclo[n]pyrrole complex. Only one peak was observed in the arrival time distributions for all complexes, and the experimental cross sections indicated that only structures with d(T(2)AG(3))(4) in an antiparallel G-quadruplex arrangement and each cyclo[n]pyrrole externally stacked below the G-quartets occur under these experimental conditions. When the cyclo[n]pyrroles were intercalated or nonspecifically bound to the quadruplex, or if conformations different than antiparallel were considered for d(T(2)AG(3))(4), the theoretical cross sections did not match experiment. On this basis, it is inferred that (1) external stacking represents the dominant binding mode for the interaction of cyclo[n]pyrroles with d(T(2)AG(3))(4) and (2) the overall size and charge of the cyclo[n]pyrroles play important roles in defining the binding strength.