Caffeoylquinic Acids,Cytotoxic, Antioxidant,Acetylcholinesterase and Tyrosinase Enzyme Inhibitory Activities of Six Inula Species from Bulgaria

Chlorogenic (5‐CQA), 1,5‐, 3,5‐, 4,5‐ and 3,4‐dicaffeoylquinic (DCQA) acids were identified and quantified in the methanol extracts of Inula oculus‐christi L., I. bifrons L., I. aschersoniana Janka var. aschersoniana, I. ensifolia L., I. conyza (Griess .) DC. and I. germanica L. by HPLC analysis. The amount of 5‐CQA varied from 5.48 to 28.44 mg/g DE and the highest content was detected in I. ensifolia. 1,5‐DCQA (4.05–55.25 mg/g DE) was the most abundant dicaffeoyl ester of quinic acid followed by 3,5‐DCQA, 4,5‐DCQA and 3,4‐DCQA. The extract of I. ensifolia showed the highest total phenolic content (119.92±0.95 mg GAE/g DE) and exhibited the strongest DPPH radical scavenging activity (69.41±0.55 %). I. bifrons extract was found to be the most active sample against ABTS^.+ (TEAC 0.257±0.012 mg/mL) and the best tyrosinase inhibitor. The studied extracts demonstrated a low inhibitory effect towards acetylcholinesterase and possessed low cytotoxicity in concentration range from 10 to 300 μg/mL toward non‐cancer (MDCK II) and cancer (A 549) cells.     

Caffeoylquinic acids: chemistry,biosynthesis, occurrence,analytical challenges,and bioactivity

Caffeoylquinic acids (CQAs) are specialized plant metabolites we encounter in our daily life. Humans consume CQAs in mg-to-gram quantities through dietary consumption of plant products. CQAs are considered beneficial for human health, mainly due to their anti-inflammatory and antioxidant properties. Recently, new biosynthetic pathways via a peroxidase-type p-coumaric acid 3-hydroxylase enzyme were discovered. More recently, a new GDSL lipase-like enzyme able to transform monoCQAs into diCQA was identified in Ipomoea batatas. CQAs were recently linked to memory improvement; they seem to be strong indirect antioxidants via Nrf2 activation. However, there is a prevalent confusion in the designation and nomenclature of different CQA isomers. Such inconsistencies are critical and complicate bioactivity assessment since different isomers differ in bioactivity and potency. A detailed explanation regarding the origin of such confusion is provided, and a recommendation to unify nomenclature is suggested. Furthermore, for studies on CQA bioactivity, plant-based laboratory animal diets contain CQAs, which makes it difficult to include proper control groups for comparison. Therefore, a synthetic diet free of CQAs is advised to avoid interferences since some CQAs may produce bioactivity even at nanomolar levels. Biotransformation of CQAs by gut microbiota, the discovery of new enzymatic biosynthetic and metabolic pathways, dietary assessment, and assessment of biological properties with potential for drug development are areas of active, ongoing research. This review is focused on the chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity recently reported for mono-, di-, tri-, and tetraCQAs.     

Ent-pimaranes, ent-kauranes,Heliangolides and other Constituents of three Helianthus species

Aerial parts of Helianthus strumosus gave the C-2′ epimer of the heliangolide 2′,3′-dihydrobudlein A as well as the flavones nevadensin, hyme     

Quinazolin‐4(3H)‐one‐Based Hydroxamic Acids: Design,Synthesis and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin‐4(3H)‐ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI?H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N‐hydroxy‐7‐(7‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5b ) and N‐hydroxy‐7‐(6‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5c ) (IC₅₀ values, 0.10–0.16 μm ) were found to be approximately 30‐fold more cytotoxic than SAHA (IC₅₀ values of 3.29–3.67 μm ). N‐Hydroxy‐7‐(4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5a ; IC₅₀ values of 0.21–0.38 μm ) was approximately 10‐ to 15‐fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC₅₀ values in sub‐micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c , strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.     

Biological Microchips with Hydrogel-Immobilized Nucleic Acids,Proteins, and Other Compounds: Properties and Applications in Genomics

The MAGIChip (MicroArrays of Gel-Immobilized Compounds on a chip) consists of an array of hydrophilic gel pads fixed on a hydrophobic glass surface. These pads of several picoliters to several nanoliters in volume contain gel-immobilized nucleic acids, proteins, and other compounds, as well as live cells. They are used to conduct chemical and enzymatic reactions with the immobilized compounds or samples bound to them. In the latter case, nucleic acid fragments can be hybridized, modified, and fractionated within the gel pads. The main procedures required to analyze nucleic acid sequences (PCR, detachment of primers and PCR-amplified products from a substrate, hybridization, ligation, and others) can be also performed within the microchip pads. A flexible, multipurpose, and inexpensive system has been developed to register the processes on a microchip. The system provides unique possibilities for research and biomedical applications, allowing one to register both equilibrium states and the course of reaction in real time. The system is applied to analyze both kinetic and thermodynamic characteristics of molecular interaction in the duplexes formed between nucleic acids and the probes immobilized within the microchip gel pads. Owing to the effect of stacking interaction of nucleic acids, the use of short oligonucleotides extends the possibilities of microchips for analysis of nucleic acid sequences, allowing one to employ the MALDI-TOF mass spectrometry to analyze the hybridization data. The specialized MAGIChips has been successfully applied to reveal single-nucleotide polymorphism of many biologically significant genes, to identify bacteria and viruses, to detect toxins and characterize the genes of pathogenic bacteria responsible for drug resistance, and to study translocations in the human genome. On the basis of the MAGIChip, protein microchips have been created, containing immobilized antibodies, antigens, enzymes, and many other substances, as well as microchips with gel-immobilized live cells.     

Bakkenolide-A. Its distribution in Petasites species and cytotoxic properties

A rapid GLC method is described for the determination of bakkenolide-A in small amounts of plant material. The distribution of bakkenolide-A among the different lipid classes of Petasites albus is discussed and also the distribution among different parts of the plant during a growing season. Smaller amounts of bakkenolide-A are found in P. hybridus buds and only trace amounts in P. fragrans.Cytotoxicity tests showed bakkenolide-A has marked cytotoxic activity and potential anti-tumour properties.     

Antimicrobial Pyridazines: Synthesis,Characterization, Cytotoxicity,Substrate Promiscuity,and Molecular Docking

A facile and convenient synthesis of new pyridazines suitable for use as antimicrobial agents was reported. The hydrazide intermediate was coupled with various benzaldehydes and/or acetophenones and cyclized instantaneously to afford target pyridazine derivatives. The structures of new pyridazines were confirmed by IR, ¹H‐ and ¹³C‐NMR, elemental analysis in addition to representative LC/MS. Antimicrobial activity was screened against 10 bacterial and fungal strains. The new pyridazines showed strong to very strong antibacterial activity against Gram‐negative (GNB) bacteria, while none of them showed significant antifungal activity at the same concentration range. Chloro derivatives exhibited the highest antibacterial activity with MICs (0.892–3.744 μg/mL) lower than that of chloramphenicol (2.019–8.078 μg/mL) against E. coli, P. aeruginosa, and S. marcescens. Prediction of ADME parameters, pharmacokinetics, and substrate promiscuity revealed that these new pyridazines could be promising drug candidates. Cytotoxic studies on rat hepatocytes showed how much safe these new pyridazines on living organisms (IC₅₀>64 μg/mL). MOE docking studies showed a good overlay of these new pyridazines with co‐crystallized ligand within an E. coli DNA gyrase subunit B active sites (4KFG).     

Quinazoline‐Based Hydroxamic Acids: Design,Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N‐hydroxybenzamides incorporating quinazoline heterocycles ( 4a  –  4i , 6a  –  6i ). Bioevaluation showed that these quinazoline‐based hydroxamic acids and N‐hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI‐H23, lung). In term of cytotoxicity, several compounds, e.g., 4g , 4c , 4g  –  4i , 6c , and 6h , displayed from 5‐ up to 10‐fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC₅₀ values in sub‐micromolar range. Some compounds, e.g., 4g , 6c , 6e , and 6h , were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g , 6c , and 6g , while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.     

Significantly Enhanced Thermoelectric Properties of PEDOT:PSS Films through Sequential Post‐Treatments with Common Acids and Bases

Thermoelectric (TE) materials are important for the sustainable development because they enable the direct harvesting of low‐quality heat into electricity. Among them, conducting polymers have attracted great attention arising from their advantages, such as flexibility, nontoxicity, easy availability, and intrinsically low thermal conductivity. In this work, a novel and facile method is reported to significantly enhance the TE property of poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) films through sequential post‐treatments with common acids and bases. Compared with the as‐prepared PEDOT:PSS, both the Seebeck coefficients and electrical conductivities can be remarkably enhanced after the treatments. The oxidation level, which significantly impacts the TE property of the PEDOT:PSS films, can also be well tuned by controlling the experimental conditions during the base treatment. The optimal PEDOT:PSS films can have a Seebeck coefficient of 39.2 µV K^?1 and a conductivity of 2170 S cm^?1 at room temperature, and the corresponding power factor is 334 µW (m^?1 K^?2). The enhancement in the TE properties is attributed to the synergetic effect of high charge mobility by the acid treatment and the optimal oxidation level tuned by the base treatment.     

Caesalpinia palmeri: First Report on the Phenolic Compounds Profile,Antioxidant and Cytotoxicity Effect

This study aimed to determine the phenolic compounds profile, antioxidant potential and cytotoxicity of extracts and fractions of Caesalpinia palmeri. Methanolic extracts were generated from C. palmeri berries, stems and flowers. The latter was subjected to liquid-liquid partition, obtaining hexane, ethyl acetate and residues fractions. Results showed that the flower extract and ethyl acetate fraction had a larger concentration of phenolic compounds (148.9 and 307.9 mg GAE/g, respectively), being ellagic acid (6233.57 and 19550.08 μg/g, respectively), quercetin-3-β-glycoside (3023.85 and 8952.55 μg/g, respectively) and gallic acid (2212.98 and 8422.34 μg/g, respectively) the most abundant compounds. Flower extract and ethyl acetate fraction also presented the highest antioxidant capacity on all tested methods (DPPH, ABTS, ORAC and FRAP) and low cytotoxicity against ARPE-19 cells (IC₅₀ >170 μg/mL). C. palmeri possessed high antioxidant potential, associated with the presence of phenolic compounds and low cytotoxicity, suggesting that they could represent an option to counter oxidative stress.     

亚氨基酸编码方法及其应用

赋予氨基酸编码方法下除终止子之外的密码子突变为终止子时每一位发生的变化权值,利用矩阵来表示所有的突变方式和难易程度,综合亲水性与疏水性理化性质,提出亚氨基酸编码方法,并给出该编码方法下同义密码子的相对使用度fSubtypesRelativeSynonymousCodonUsage,SRSCU）．然后选取15条H5N1序列,使用MEGA4．0分析它们的同源性,并分别在氨基酸编码、拟氨基酸编码、亚氨基酸编码这三种环境下研究所选序列使用密码子的偏好性,对比结果验证,亚氨基酸编码方法具有相应的优越性．     

Flavonoid chemistry,chromosome number and phylogenetic relationships of Helenium chihuahuensis

Five populations of Helenium chihuahuensis were examined for flavonoid content, chromosome number and morphological characteristics. Thirteen flavonoid compounds were detected of which eleven were at least partially identified and were found to be flavones. The chromosome number was determined to be $\text{2}\text{n}\text{= 15II}$. Helenium arizonicum also was found to have a chromosome number of $\text{2}\text{n}\text{= 15II}$. Helenium chihuahuensis, H. arizonicum, H. mexicanum and H. laciniatum were compared by constructing Wagner Networks, both excluding and including flavonoid data, in order to clarify their phylogenetic relationships.     

Cytotoxicity of two new ribosome-inactivating proteins,cinnamomin and camphorin,to carcinoma cells

Cinnamomin (two-chain) and camphorin (single-chain), two novel ribosome-inactivating proteins (RIPs) purified from the seeds of Cinnamomum camphora, produced inhibitory effects in cultured carcinoma cells. The IC₅₀ of cinnamomin to the human hepatocarcinoma cell-line 7721 and the melanoma cell-line M21 were 18·8 nmol and 11·7 nmol respectively. The IC₅₀ of camphorin to the human hepatocarcinoma cell-line 7721 was 59 nmol, whereas the melanoma cell-line M21 was not susceptible to camphorin. Furthermore, cinnamomin exhibited a remarkable inhibitory effect on the growth of solid melanoma in the skin of the nude mouse. An R-fragment could be isolated from ribosomes of cinnamomin- or camphorin-treated carcinoma cells after incubation with acidic aniline, indicating that the cytotoxicity of these two new RIPs to carcinoma cells might result from modification to the ribosomes.     

4α,15-Dihydroencelin and related sesquiterpene acids from perymenium featherstonei

Perymenium featherstonei afforded, in addition to the known ent-kaurene derivative 4α, 15-dihydroencelin, two closely related epimeric acids.     

Simultaneous RP‐HPLC‐DAD Separation,and Determination of Flavonoids and Phenolic Acids in Plantago L. Species

A rapid reversed‐phase (RP) high‐performance liquid chromatography method was developed and applied for simultaneous separation, and determination of flavonoids and phenolic acids in eight Plantago L. taxa (P. altissima L., P. argentea Chaix , P. coronopus L., P. holosteum Scop . ssp. depauperata Pilger , P. holosteum ssp. holosteum, P. holosteum ssp. scopulorum (Degen) Horvati? , P. lagopus L., and P. maritima L.) growing in Croatia. Chromatographic separation was carried out on Zorbax Eclipse XDB‐C18 using gradient elution with a H₂O (pH 2.5, adjusted with CF₃COOH) and MeCN mixture at 30°. The contents of analyzed phenolic compounds (% of the dry weight of the leaves, dw) varied among examined species: rutin (max. 0.024%, P. argentea), hyperoside (max. 0.020%, P. lagopus), quercitrin (max. 0.013%, P. holosteum ssp. holosteum), quercetin (max. 0.028%, P. holosteum ssp. scopulorum), chlorogenic acid (max. 0.115%, P. lagopus), and caffeic acid (max. 0.046%, P. coronopus). Isoquercitrin was detected only in P. argentea (0.020%), while isochlorogenic acid content was below limit of quantification in all investigated species. Multivariate analyses (UPGMA and PCA) showed significant differences in contents of investigated polyphenolic compounds between different Plantago taxa. Accordingly, investigated substances might be employed as chemotaxonomic markers in the study of the complex genus Plantago.     

Enantiomeric Separation of Underivatized Amino Acids: Predictability of Chiral Recognition on Ristocetin A Chiral Stationary Phase

The present work aimed to investigate the predictability of the chromatographic behavior for the separation of underivatized amino acids on ristocetin A, known as Chirobiotic R, using a DryLab high‐performance liquid chromatography (HPLC) method development software, which is typically used to predict the effect of changing various chromatographic parameters on resolution in the reversed phase mode. After implementing the basic runs, and judging the predictability via the computed resolution map, it can be deduced that the chiral recognition mechanisms tend towards a hydrophilic interaction chromatography rather than the reversed phase mode, which limits the ability of DryLab software to predict separations on Chirobiotic R. Chirality 26:132–135, 2014. © 2014 Wiley Periodicals, Inc.     

神经肽注射液氨基酸组成分析及含量测定方法的研究

本文采用具有高灵敏度的高效液相色谱法（ＨＰＬＣ）对神经肽注射液中的氨基酸组成及含量进行了测定,结果表明该注射液中含有１３种游离氨基酸（２９．９４ｍｇ／１００ｍｌ）和大量的低分子多肽（２１１．１６ｍｇ／１００ｍｌ）。同时,本文也建立了简便快速测定神经肽注射液中溶质含量的紫外分光光度法（ＵＶＳ）。试验结果反映了产品的内在质量,为建立质量控制方法提供了依据。     

Synchrotron-Based FTIR Spectromicroscopy: Cytotoxicity and Heating Considerations

Synchrotron radiation-based Fouriertransform infrared (SR-FTIR)spectromicroscopy is a newly emergingbioanalytical and imaging tool. This uniquetechnique provides mid-infrared (IR)spectra, hence chemical information, withhigh signal-to-noise at spatial resolutionsas fine as 3 to 10 microns. Thus it enablesresearchers to locate, identify, and trackspecific chemical events within anindividual living mammalian cell. Mid-IRphotons are too low in energy (0.05–0.5eV) to either break bonds or to causeionization. In this review, we show thatthe synchrotron IR beam has no detectableeffects on the short- and long-termviability, reproductive integrity,cell-cycle progression, and mitochondrialmetabolism in living human cells, andproduces only minimal sample heating (<0.5°C). These studies haveestablished an important foundation forSR-FTIR spectromicroscopy in biological andbiomedical research.