Flavonoids as chemosystematic markers in the tribe Cichorieae of the Asteraceae

This review summarizes reports on flavonoids from the Cichorieae (Lactuceae) tribe of the Asteraceae family. A total of 135 different compounds have been reported from 354 taxa belonging to 299 species, including many cultivars of common vegetables like chicory and lettuce. The reported compounds encompass flavanones (11 compounds), flavanonols (2 compounds), flavones (72 compounds), flavonols (35 compounds), anthocyanidins (9 compounds), isoflavonoids (2 compounds), chalcones (3 compounds), and an aurone. So far only 43 of the approximately 100 currently recognized genera of the tribe Cichorieae have been investigated for the occurrence of flavonoids. The distribution of the various classes of flavonoids is analyzed with regards to data from the current molecular-based reassessment of the systematics of the tribe.     

Detection of organic compounds on Mars]

McKay et al. detected polycyclic aromatic hydrocarbons (PAHs) in Martian meteorite ALH 84001 by two-step laser mass spectrometry. From the presence of PAHs, together with other results, they concluded that there were past life of Mars. On the other hands, no organisms nor organic compounds were detected in Martian regolith in Viking experiments in 1976. In order to obtain solid evidence for organisms or bioorganic compounds compounds on Mars, further analyses of Martian samples are required. There may be four classes of organic compounds on Mars, which are (i) organic compounds abiotically formed from primitive Mars atmosphere, (ii) Organic compounds delivered out of Mars, (iii) Organic compounds biotically formed by Mars organisms, and (iv) Organic compounds abiotically formed from the present Mars atmosphere. Possible organic compounds on Mars and analytical methods for them are discussed.     

Medicinal applications of heavy-metal compounds

A brief summary of the key role for certain heavy-metal compounds in medicine is discussed, with a special focus on very recent findings in the following four topics: platinum anti-tumor compounds (novel mononuclear compounds, dinuclear compounds and trinuclear compounds with promising activity); ruthenium anti-tumor compounds (the first clinical trial for a Ru compound has begun); gadolinium NMR-imaging compounds (association with biomacromolecules is now possible); technetium compounds (the use of organometallic precursors opens a plethora of new species and enables the labeling of, for example, neurotransmitter molecules).     

HS-SPME & GC-MS分析印加果种子的挥发性物质

利用顶空固相微萃取-气相色谱质谱法(HS-SPME & GC-MS)分析印加果Plukenetia volubilis近成熟种子的挥发性物质,通过面积归一法计算出各成分的相对含量。结果共分离鉴定出64种化学成分,其中6种酯类化合物,占45.86%;12种醇类化合物,占27.71%;7种烯烃类化合物,占6.71%;9种醛类化合物,占3.89%;6种酮类化合物,占2.78%;16种烷烃类化合物,占1.78%。此外,盐酸氨基脲占5.47%,氨基脲占3.25%,还有1.51%三氯乙酸和0.23%甲基异丙基苯及其他化合物。     

Synthesis, structural elucidation, DNA-PK inhibition, homology modelling and anti-platelet activity of morpholino-substituted-1,3-naphth-oxazines

A number of new angular 2-morpholino-(substituted)-naphth-1,3-oxazines (compound 10b), linear 2-morpholino-(substituted)-naphth-1,3-oxazines (compounds 13b-c), linear 6, 7 and 9-O-substituted-2-morpholino-(substituted)-naphth-1,3-oxazines (compounds 17-22, 24, and 25) and angular compounds 14-16 and 23 were synthesised. The O-substituent was pyridin-2yl-methyl (15, 18, and 21) pyridin-3yl-methyl (16, 19, and 22) and 4-methylpipreazin-1-yl-ethoxy (23-25). Twelve compounds were tested for their inhibitory effect on collagen induced platelet aggregation and it was found that the most active compounds were compounds 19 and 22 with IC(50)=55±4 and 85±4 μM, respectively. Furthermore, the compounds were also assayed for their ability to inhibit DNA-dependent protein kinase (DNA-PK) activity. The most active compounds were 18 IC(50)=0.091 μM, 24 IC(50)=0.191 μM, and 22 IC(50)=0.331 μM. Homology modelling was used to build a 3D model of DNA-PK based on the X-ray structure of phosphatidylinositol 3-kinases (PI3Ks). Docking of synthesised compounds within the binding pocket and structure-activity relationships (SAR) analyses of the poses were performed and results agreed well with observed activity.     

Susceptibility and resistance of ruminal bacteria to antimicrobial feed additives

Susceptibility and resistance of ruminal bacterial species to avoparcin, narasin, salinomycin, thiopeptin, tylosin, virginiamycin, and two new ionophore antibiotics, RO22-6924/004 and RO21-6447/009, were determined. Generally, antimicrobial compounds were inhibitory to gram-positive bacteria and those bacteria that have gram-positive-like cell wall structure. MICs ranged from 0.09 to 24.0 micrograms/ml. Gram-negative bacteria were resistant at the highest concentration tested (48.0 micrograms/ml). On the basis of their fermentation products, ruminal bacteria that produce lactic acid, butyric acid, formic acid, or hydrogen were susceptible and bacteria that produce succinic acid or ferment lactic acid were resistant to the antimicrobial compounds. Selenomonas ruminantium was the only major lactic acid-producing bacteria resistant to all the antimicrobial compounds tested. Avoparcin and tylosin appeared to be less inhibitory (MIC greater than 6.0 micrograms/ml) than the other compounds to the two major lactic acid-producing bacteria, Streptococcus bovis and Lactobacillus sp. Ionophore compounds seemed to be more inhibitory (MIC, 0.09 to 1.50 micrograms/ml) than nonionophore compounds (MIC, 0.75 to 12.0 micrograms/ml) to the major butyric acid-producing bacteria. Treponema bryantii, an anaerobic rumen spirochete, was less sensitive to virginiamycin than to the other antimicrobial compounds. Ionophore compounds were generally bacteriostatic, and nonionophore compounds were bactericidal. The specific growth rate of Bacteroides ruminicola was reduced by all the antimicrobial compounds except avoparcin. The antibacterial spectra of the feed additives were remarkably similar, and it appears that MICs may not be good indicators of the potency of the compounds in altering ruminal fermentation characteristics.     

High-throughput determination of identity, purity, and quantity of combinatorial library members using LC/MS/UV/ELSD

We have used a high-throughput LC/MS/UV/ELSD method to rapidly determine the absolute quantity and purity of 42 organic compounds from seven lead discovery libraries. A general calibration curve generated from a different set of 42 compounds with seven different scaffolds was used in this analysis. We have also studied 33 organic compounds with different molecular weight (MW) by LC/MS/UV/ELSD to investigate the effect of MW on ELSD response and the accuracy for purity and quantity measurement using UV(214) and ELSD. A general ELSD calibration curve from these compounds was also generated to quantify 42 library compounds. Purity measurement by ELSD underestimates the amounts of impurities due to a reduced ELSD response from smaller molecular weight impurities often produced in library synthesis. Absolute quantity determination by ELSD is more accurate (RSD 28%) than that by UV(214) (48%) using a calibration curve generated from the same set of compounds with diverse MWs. Error assessment for the measurement of absolute quantity of a class of commercial compounds and a class of representing reference compounds from seven diverse lead discovery libraries shows that structurally related compounds should be used to generate calibration curves to sustain smaller deviation.     

Susceptibility and resistance of ruminal bacteria to antimicrobial feed additives.

Susceptibility and resistance of ruminal bacterial species to avoparcin, narasin, salinomycin, thiopeptin, tylosin, virginiamycin, and two new ionophore antibiotics, RO22-6924/004 and RO21-6447/009, were determined. Generally, antimicrobial compounds were inhibitory to gram-positive bacteria and those bacteria that have gram-positive-like cell wall structure. MICs ranged from 0.09 to 24.0 micrograms/ml. Gram-negative bacteria were resistant at the highest concentration tested (48.0 micrograms/ml). On the basis of their fermentation products, ruminal bacteria that produce lactic acid, butyric acid, formic acid, or hydrogen were susceptible and bacteria that produce succinic acid or ferment lactic acid were resistant to the antimicrobial compounds. Selenomonas ruminantium was the only major lactic acid-producing bacteria resistant to all the antimicrobial compounds tested. Avoparcin and tylosin appeared to be less inhibitory (MIC greater than 6.0 micrograms/ml) than the other compounds to the two major lactic acid-producing bacteria, Streptococcus bovis and Lactobacillus sp. Ionophore compounds seemed to be more inhibitory (MIC, 0.09 to 1.50 micrograms/ml) than nonionophore compounds (MIC, 0.75 to 12.0 micrograms/ml) to the major butyric acid-producing bacteria. Treponema bryantii, an anaerobic rumen spirochete, was less sensitive to virginiamycin than to the other antimicrobial compounds. Ionophore compounds were generally bacteriostatic, and nonionophore compounds were bactericidal. The specific growth rate of Bacteroides ruminicola was reduced by all the antimicrobial compounds except avoparcin. The antibacterial spectra of the feed additives were remarkably similar, and it appears that MICs may not be good indicators of the potency of the compounds in altering ruminal fermentation characteristics.     

Microbial degradation of pollutants at high salt concentrations

Though our knowledge on microbial degradation of organic pollutants at high salt concentrations is still limited, the list of toxic compounds shown to be degraded or transformed in media of high salinity is growing. Compounds transformed aerobically include saturated and aromatic hydrocarbons (by certain archaeobacteria), certain aromatic compounds, organophosphorus compounds, and formaldehyde (by halotolerant eubacteria). Anaerobic microbial transformations of toxic compounds occurring at high salt concentrations include reduction of nitroaromatic compounds, and possibly transformation of chlorinated aromatic compounds.     

Cytotoxicity, cell cycle arrest, antioxidant activity and interaction of dibenzoxanthenes derivatives with DNA

In this study, we report the DNA interaction and cytotoxicity of four dibenzoxanthene compounds 1-4. The binding behaviors of these compounds to calf thymus DNA were studied by absorption titration, viscosity measurements. The DNA binding constants of compounds 1, 2, 3, and 4 are 5.05×10(4), 2.13×10(3), 5.10×10(4), and 3.03×10(3) M(-1), respectively. The lipophilicity of the compounds was determined by the shake flask method. The cytotoxicity of these compounds has been assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. These compounds exhibit high activity against BEL-7402, Hela, MG-63, and SKBR-3 cells. The cell cycle arrest was analyzed by flow cytometry. These compounds inhibit S phase of BEL-7402 and SKBR-3 cells. The experiments on antioxidant activity show that these compounds exhibit good antioxidant activity against hydroxyl radical ((?)OH).     

细菌吸附及转运芳香族化合物的研究进展

芳香族化合物是一类具有苯环结构的有机物,它们结构稳定,不易分解,并可通过食物链进行生物富集和生物放大,对生态环境及人类健康造成极大危害。细菌具有超强的分解代谢能力,能降解多环芳烃(polycyclic aromatic hydrocarbons, PAHs)等多种难降解芳香族污染物。吸附和转运是细菌进行芳香族化合物细胞内代谢的前提。虽然芳香族化合物的细菌降解已取得较为显著的研究进展,但吸附和转运机理仍不甚清楚。本文讨论了细菌对芳香族化合物的吸附有积极作用的细胞表面疏水性、生物被膜形成和细菌趋化性等影响因素,总结了FadL家族、TonB依赖性受体蛋白、OmpW家族等外膜转运系统和主要协同转运蛋白超家族(major facilitator superfamily, MFS)转运体、ATP结合盒(ATP-binding cassette, ABC)转运蛋白等内膜转运系统对该类化合物跨膜运输作用,并对跨膜转运机制进行了讨论和阐述,旨在为芳香族污染物的防控和治理提供一定理论参考。     

How do herbivorous insects cope with noxious secondary plant compounds in their diet?

Herbivorous insects use a variety of physiological mechanisms to cope with noxious (i.e., unpalatable and/or toxic) compounds in their food plants. Here, I review what is known about this coping process, focusing on one species of caterpillar, the tobacco hornworm (Manduca sexta). Herbivorous insects possess both preingestive (i.e., chemosensory) and postingestive response mechanisms for detecting plant secondary compounds. Stimulation of either class of detection mechanism inhibits feeding rapidly by reducing biting rate and/or bite size. This aversive response is highly adaptive during encounters with secondary plant compounds that are toxic. The insect's dilemma is that many harmless or mildly toxic compounds also activate the aversive response. To overcome this dilemma, herbivorous insects employ at least three mechanisms for selectively deactivating their aversive response to relatively harmless secondary plant compounds: (1) the presence of carbohydrates can mask the unpalatable taste of some secondary plant compounds; (2) prolonged dietary exposure to some unpalatable secondary plant compounds can initiate long-term adaptation mechanisms in the peripheral and central gustatory system; and (3) dietary exposure to toxic compounds can induce production of P450 detoxication enzymes. Thus, herbivorous insects utilize an integrated suite of physiological mechanisms to detect potentially toxic compounds in foods, and then selectively adapt to those that do not pose a serious threat to their growth and survivorship.     

Plant-Derived Enzymes Producing Chiral Aroma Compounds and Potential Application

Aroma (volatile) compounds play important ecological functions in plants, and also contribute to the quality of plant-derived foods. Moreover, chiral aroma compounds affect their functions in plants and lead to different flavor quality properties. Formations of chiral aroma compounds are due to the presence of enzymes producing these compounds in plants, which are generally involved in the final biosynthetic step of the aroma compounds. Here, we review recent progress in research on the plant-derived enzymes producing chiral aroma compounds, and their changes in response to environmental factors. The chiral aroma enzymes that have been reported produce (R)-linalool, (S)-linalool, (R)-limonene, and (S)-limonene, etc., and these enzymes are found in various plant species. We also discuss the origins of enantioselectivity in the plant-derived enzymes producing chiral aroma compounds and summarize the potential use of plants containing enzymes producing chiral aroma compounds for producing chiral flavors/fragrances.     

Role of hydrophobicity on the monoamine receptor binding affinities of central nervous system drugs: a quantitative retention-activity relationships analysis using biopartitioning micellar chromatography

Biological action and activity reflect an aspect of the fundamental physicochemical properties of the bioactive compounds. As an alternative to classical QSAR studies, in this work different quantitative retention-activity relationships (QRAR) models are proposed, which are able to describe the role of hydrophobicity on the binding affinity to different brain monoamine receptors (H(1)-histamine, alpha(1)-noradrenergic and 5-HT(2)-serotonergic) of different families of psychotherapeutic drugs. The retention of compounds is measured in a biopartitioning micellar chromatography (BMC) system using Brij-35 mobile phases. The adequacy of the QRAR models developed is due to the fact that both the retention of compounds in BMC and the drug-receptor interaction are described by the same hydrophobic, electronic and steric properties of compounds. The obtained results indicate that, for structurally related compounds that present the same molecular features as the basic pharmacophore, there is a retention range in which compounds present the highest affinity to all of monoamine receptors.     

Effect of water and temperature stress on the content of active constituents of Hypericum brasiliense Choisy.

Hypericum brasiliense is a medicinal herb containing several compounds with important pharmacological activity. In this study, we investigated the effects of water stress (waterlogging and drought) and temperature (low and high, constant and alternate) on the content of betulinic acid and phenolic compounds (quercetin, rutin, 1,5-dihydroxyxanthone, isouliginosin B) in this species. In general, the water stress increased the levels of all of the compounds analyzed, particularly some of the phenolic compounds. On the other hand, the responses to alternating temperatures varied according to the compound. The results for plants kept in growth chambers indicated that low light intensity might have influenced the levels of the compounds. There was also a reallocation of carbon, with water-stressed plants showing a reduction in growth while the levels of the compounds increased. In the temperature treatments, such an increase was evident only for the phenolic compounds.     

Inhibitors of protein geranylgeranyltransferase I and Rab geranylgeranyltransferase identified from a library of allenoate-derived compounds

Protein geranylgeranylation is critical for the function of a number of proteins such as RhoA, Rac, and Rab. Protein geranylgeranyltransferase I (GGTase-I) and Rab geranylgeranyltransferase (RabGGTase) catalyze these modifications. In this work, we first describe the identification and characterization of small molecule inhibitors of GGTase-I (GGTI) with two novel scaffolds from a library consisting of allenoate-derived compounds. These compounds exhibit specific inhibition of GGTase-I and act by competing with a substrate protein. Derivatization of a carboxylic acid emanating from the core ring of one of the GGTI compounds dramatically improves their cellular activity. The improved GGTI compounds inhibit proliferation of a variety of human cancer cell lines and cause G(1) cell cycle arrest and induction of p21(CIP1/WAF1). We also report the identification of novel small molecule inhibitors of RabGGTase. These compounds were identified first by screening our GGTI compounds for those that also exhibited RabGGTase inhibition. This led to the discovery of a common structural feature for RabGGTase inhibitors: the presence of a characteristic six-atom aliphatic tail attached to the penta-substituted pyrrolidine core. Further screening led to the identification of compounds with preferential inhibition of RabGGTase. These compounds inhibit RabGGTase activity by competing with the substrate protein. These novel compounds may provide valuable reagents to study protein geranylgeranylation.     

Novel selective anti-androgens with a diphenylpentane skeleton

We have proposed a multi-template approach for drug development, focusing on similar fold structures of proteins, and have effectively generated lead compounds for several drug targets. Modification of these polypharmacological lead compounds is then needed to generate target-selective compounds. In the work presented here, we aimed at separation of the anti-androgen activity and vitamin D activity of previously identified diphenylpentane lead compounds. Based on the determined X-ray crystal structures of androgen receptor and vitamin D receptor, bulky substituents were introduced at the t-butyl group in the lead compounds 2 and 3. As a result of this structural development, we obtained 16c, which exhibits more potent anti-androgen activity (IC(50): 0.13 μM) than clinically used anti-androgen bicalutamide (IC(50): 0.67 μM) with 30-fold selectivity over vitamin D activity. This result indicates that lead compounds obtained via the multi-template approach can indeed be structurally modified to generate target-selective compounds.     

Sesquiterpene lactones and their precursors as chemosystematic markers in the tribe Cichorieae of the Asteraceae

This review summarizes all reports on sesquiterpene lactones and their immediate precursors from the Cichorieae (Lactuceae) tribe of the Asteraceae. A total of 360 compounds have been reported from this tribe. The reported substances belong to three classes of sesquiterpenoids: guaianolides (243 compounds), eudesmanolides (73 compounds), and germacranolides (44 compounds). Sources of these compounds encompass 139 taxa from 31 different genera. The distribution of these lactones within the tribe Cichorieae is discussed in a chemosystematic context. Moreover, some general ideas about the interpretation of chemosystematic data are discussed.     

Synthesis and biological evaluation of novel quinazoline-triazole hybrid compounds with potential use in Alzheimer’s disease

A library of twelve quinazoline-triazole hybrid compounds were designed, synthesized and evaluated as a novel class of acetylcholinesterase inhibitors to treat Alzheimer’s disease (AD). The biological assay results demonstrated the ability of several hybrid compounds to inhibit AChE enzyme (IC₅₀ range = 0.2–83.9 µM). To understand the high potential activity of these compounds, molecular docking simulations were performed to get better insights into the mechanism of binding of quinazoline-triazole hybrid compounds. As expected, compounds 8a and 9a-b bind to both catalytic anionic site (CAS) and peripheral anionic site (PAS) in the active site of AChE enzyme, which implicates that these compounds could act as dual binding site inhibitors. These compounds were not cytotoxic and they also displayed appropriated physicochemical as well as pharmacokinetic profile to be developed as novel anti-AD drug candidates.