Chemical diversification trends in Astragalus caprinus (Leguminosae), based on the flavonoid pathway

Flavonoid glycosides of Astragalus caprinus (Leguminosae) were investigated; more than 30 glycosides were found in leaf material, based on the aglycones kaempferol, quercetin and their methylated derivatives. Among them 14 compounds were found in significant amounts and showed a contrasting distribution. They could be ordered into three groups: polyglycosides, acylated polyglycosides and methylated polyglycosides. The distribution of these compounds was studied within a large collection of individual plants harvested in Tunisia; the results showed a relationship between metabolic trends and ecological diversification.     

Bi-functional peptides with both trypsin-inhibitory and antimicrobial activities are frequent defensive molecules in Ranidae amphibian skins

Amphibian skins act as the first line against noxious aggression by microorganisms, parasites, and predators. Anti-microorganism activity is an important task of amphibian skins. A large amount of gene-encoded antimicrobial peptides (AMPs) has been identified from amphibian skins. Only a few of small protease inhibitors have been found in amphibian skins. From skin secretions of 5 species (Odorrana livida, Hylarana nigrovittata, Limnonectes kuhlii, Odorrana grahami, and Amolops loloensis) of Ranidae frogs, 16 small serine protease inhibitor peptides have been purified and characterized. They have lengths of 17-20 amino acid residues (aa). All of them are encoded by precursors with length of 65-70 aa. These small peptides show strong trypsin-inhibitory abilities. Some of them can exert antimicrobial activities. They share the conserved GCWTKSXXPKPC fragment in their primary structures, suggesting they belong to the same families of peptide. Signal peptides of precursors encoding these serine protease inhibitors share obvious sequence similarity with those of precursors encoding AMPs from Ranidae frogs. The current results suggest that these small serine protease inhibitors are the common defensive compounds in frog skin of Ranidae as amphibian skin AMPs.     

Luminescence and fluorescence of essential oils. Fluorescence imaging in vivo of wild chamomile oil

Essential oils are currently of great importance to pharmaceutical companies, cosmetics producers and manufacturers of veterinary products. They are found in perfumes, creams, bath products, and household cleaning substances, and are used for flavouring food and drinks. It is well known that some of them act on the respiratory apparatus. The increasing interest in optical imaging techniques and the development of related technologies have made possible the investigation of the optical properties of several compounds. Luminescent properties of essential oils have not been extensively investigated. We evaluated the luminescent and fluorescent emissions of several essential oils, in order to detect them in living organisms by exploiting their optical properties. Some fluorescent emission data were high enough to be detected in dermal treatments. Consequently, we demonstrated how the fluorescent signal can be monitored for at least three hours on the skin of living mice treated with wild chamomile oil. The results encourage development of this technique to investigate the properties of drugs and cosmetics containing essential oils.     

Alkaloids of Solanaceae (nightshade plants)

Alkaloids are nitrogen containing compounds found in many plants. They are products of plants secondary metabolism derived from amino acids, purines, pyrimidines or terpene. Most of them are drugs. The biological activity of some alkaloids has led to their intensive exploitation by humans, as pharmaceuticals, narcotics or poisons. During the past 30 years, major technical advances have led to substantial progress in our understanding of alkaloid biochemistry, but since then biosynthetic pathways of some alkaloids are not explained. The nightshade (Solanaceae) are widespread family of plants containing tropane alkaloids or glycoalkaloids. Both of them are naturally produced, as a defense mechanism against insects, predator and disease. On the other hand, most of the species of Solanaceae family have been used by human since several centuries.     

新的天然免疫保护分子——PLUNC家族蛋白

在呼吸道上皮与消化道上皮的表面,覆盖有一层由免疫保护分子所组成的蛋白质混合物,在上皮组织与外界各种信号之间,它们起着信号传递中介与信号执行分子的作用.我们新克隆的NASG基因为这一混合物添加了新的成员,对其结构与功能分析表明:它属于腭、肺及鼻咽上皮克隆（PLUNC）家族中SPLUNC1的全新转录本.目前发现人类PLUNC家族至少有8个以上成员,分布在人类20号染色体大约300 kb的狭窄区域,它们具有杀菌\渗透增强蛋白结构域,在进化上高度保守,每个成员分别在呼吸道上皮的不同部位特异性表达,具有潜在的结合细菌脂多糖的功能,能对外来物理及化学刺激做出反应,以分泌蛋白的形式进入鼻咽分泌物或唾液中,部分家族成员可能具有抗微生物、清除有害化学物质、抗肿瘤等多重功效.以上说明,PLUNC家族可能是上呼吸道的一种新的天然免疫保护分子,在维持上呼吸道的正常生理活动中起重要作用.     

Gluconobacter in biosensors: applications of whole cells and enzymes isolated from gluconobacter and acetobacter to biosensor construction

Bacteria belonging to the genus Acetobacter and Gluconobacter, and enzymes isolated from them, have been extensively used for biosensor construction in the last decade. Bacteria used as a biocatalyst are easy to prepare and use in amperometric biosensors. They contain multiple enzyme activities otherwise not available commercially. The range of compounds analyzable by Gluconobacter biosensors includes: mono- and poly-alcohols, multiple aldoses and ketoses, several disaccharides, triacylglycerols, and complex parameters like utilizable saccharides or biological O₂ demand. Here, the recent trends in Gluconobacter biosensors and current practical applications are summarized. An erratum to this article can be found at     

葡萄酒中重要挥发性硫化物的代谢及基因调控

葡萄酒中的挥发性硫化物是由酿酒微生物在葡萄酒发酵过程中代谢所产生的,主要包括硫化氢、硫醇、硫醚、硫醇酯、含硫杂醇油及杂环化合物等,它们对葡萄酒的风味会产生重要影响。本综述介绍了葡萄酒中重要的挥发性硫化物的主要代谢途径及相关基因的调控机制,并提出酿酒微生物的相关研究是提高优良风味物质含量,同时抑制不良风味产生的有效途径。     

Molecular cross-talk between sponge host and associated microbes

Marine organisms especially those that live sessile, as sponges, are well known to have specific relationships with a great variety of microorganisms including bacteria and fungi. As most simple metazoan phylum, the Porifera, which emerged first during the transition from the non-Metazoa to the Metazoa from the common ancestor, comprise wide arrays of recognition molecules, both for Gram-negative bacteria and for Gram-positive bacteria as well as for fungi. They react specifically with effector molecules to inhibit or kill the invading microorganisms. The elicitation and the subsequent effector reactions of the sponges towards these microbes are outlined. However, besides of the elimination of bacteria and fungi, some of those taxa are kept as symbionts of the sponges, allowing them, for example, to accumulate the essential element manganese or to synthesize carotinoids. The sponges produce low-molecular-weight bioactive compounds, secondary metabolites, to eliminate the microorganisms. In addition, they are armed with cationic antimicrobial peptides allowing them to defend against invasive microorganisms and, in parallel, to kill or repel also metazoan invaders. The broad range of chemically and functionally different compounds qualifies the Porifera as the most important animal phylum to be exploited as a source for the isolation of new potential drugs. First molecular biological strategies have been outlined to obtain those compounds in a sustainable way, by producing them recombinantly.     

The Chemical Constituents of Glycyrrhiza aspera Root

The chemical constituents of the root of GlYcyrrhiza aspera Pall. collected in Xinjiang Autonomous Region of China were studied. Seven compounds were isolated and identified, They are glycyrrhizic acid, liquiritin, isoliquiritin, glycycoumarin, isoglycycoumarin, glycyrol and isoglycyrol. The structures of these compounds were elucidated by spectroscopic methods and chemical transformation. They were all isolated from G. aspera for the first time, among them isoglycycoumarin is a new compound, its structure was proved to be 3-(2’,4’-dihydro-xyphenyl), 5-methoxyl, 6,7-(6’,6’-dimethyl pyrano) coumarin.     

四氢蒽醌类化合物结构及其生物活性研究进展

四氢蒽醌类化合物是一类比较少见的天然结构,以微生物次生代谢产物居多,少量来源于植物,具有细胞毒活性、抗菌活性、抗疟原虫等生物活性。本文主要从四氢蒽醌类化合物及其衍生物的结构和生物活性两方面来对天然四氢蒽醌化合物进行综述,共综述了54个四氢蒽醌类化合物,45个来源于微生物,9个来源于植物南山花的根中,其中altersolanol A具有很好的抗肿瘤活性,是一个有很大吸引力的抗癌先导化合物。通过对四氢蒽醌类化合物的综述,为四氢蒽醌类化合物的进一步研究和开发提供依据。     

Properties of retinoids

Retinoids are unstable compounds being readily oxidized and/or isomerized to altered compounds, especially in the presence of oxidants including air, light, and excessive heat. They are labile toward strong acids and solvents that have dissolved oxygen or peroxides. In this review, procedures for handling and storage of retinoids and biological samples containing them have been described. The physical and chemical properties of retinoids have been reported. Simplified procedures for derivatizations and purification, and methods for quantitation of retinoids have been presented.     

Tirucallane triterpenes from the leaf extract of Entandrophragma angolense

From the leaves of Entandrophragma angolense, three triterpenoidal compounds were isolated and structurally elucidated by mass and NMR spectroscopy. They belong to the tirucallane group but two of them possess the rare seco-ring-A feature. The phytochemical data are discussed from a chemotaxonomic and biogenetic points of view.     

Screening a library of 1600 adamantyl ureas for anti-Mycobacterium tuberculosis activity in vitro and for better physical chemical properties for bioavailability

Adamantyl ureas were previously identified as a group of compounds active against Mycobacterium tuberculosis in culture with minimum inhibitor concentrations (MICs) below 0.1 μg/ml. These compounds have been shown to target MmpL3, a protein involved in secretion of trehalose mono-mycolate. They also inhibit both human soluble epoxide hydrolase (hsEH) and M. tuberculosis epoxide hydrolases. However, active compounds to date have high cLogP's and are poorly soluble, leading to low bioavailability and thus limiting any therapeutic application. In this study, a library of 1600 ureas (mostly adamantyl ureas), which were synthesized for the purpose of increasing the bioavailability of inhibitors of hsEH, was screened for activity against M. tuberculosis. 1-Adamantyl-3-phenyl ureas with a polar para substituent were found to retain moderate activity against M. tuberculosis and one of these compounds was shown to be present in serum after oral administration to mice. However, neither it, nor a closely related analog, reduced M. tuberculosis infection in mice. No correlation between in vitro potency against M. tuberculosis and the hsEH inhibition were found supporting the concept that activity against hsEH and M. tuberculosis can be separated. Also there was a lack of correlation with cLogP and inhibition of the growth of M. tuberculosis. Finally, members of two classes of adamantyl ureas that contained polar components to increase their bioavailability, but lacked efficacy against growing M. tuberculosis, were found to taken up by the bacterium as effectively as a highly active apolar urea suggesting that these modifications to increase bioavailability affected the interaction of the urea against its target rather than making them unable to enter the bacterium.     

The roles of plant phenolics in defence and communication during Agrobacterium and Rhizobium infection

Phenolics are aromatic benzene ring compounds with one or more hydroxyl groups produced by plants mainly for protection against stress. The functions of phenolic compounds in plant physiology and interactions with biotic and abiotic environments are difficult to overestimate. Phenolics play important roles in plant development, particularly in lignin and pigment biosynthesis. They also provide structural integrity and scaffolding support to plants. Importantly, phenolic phytoalexins, secreted by wounded or otherwise perturbed plants, repel or kill many microorganisms, and some pathogens can counteract or nullify these defences or even subvert them to their own advantage. In this review, we discuss the roles of phenolics in the interactions of plants with Agrobacterium and Rhizobium.     

Alkaliphilic bacteria: applications in industrial biotechnology

Alkaliphiles are interesting groups of extremophilic organisms that thrive at pH of 9.0 and above. Many of their products, in particular enzymes, have found widespread applications in industry, primarily in the detergent and laundry industries. While the enzymes have been a runaway success from the industrial point of view, many more products have been reported from alkaliphiles such as antibiotics and carotenoids. Less known are their potential for degradation of xenobiotics. They also play a key role in biogeocycling of important inorganic compounds. This review provides an insight into the huge diversity of alkaliphilic bacteria, the varied products obtained from them, and the need for further investigations on these interesting bacteria.     

Ganodermasides C and D, two new anti-aging ergosterols from spores of the medicinal mushroom Ganoderma lucidum

Two new anti-aging compounds, ganodermasides C and D, were isolated and their structures elucidated. They are novel ergosterols possessing a 4,6,8(14),22-tetraene-3-one unit with unique hydroxylation at C-9. Both of them significantly extended the replicative lifespan of the K6001 yeast strain. Ganodermasides C and D regulated the expression of the gene for UTH1 to prolong the replicative lifespan of yeast.     

Benzo[f]naphtyridones: a new family of topical antibacterial agents active on multi-resistant Gram-positive pathogens

The synthesis and antibacterial activity of benzo[f][1,7]naphtyridone derivatives are reported. These compounds are potent antibacterial agents with a Gram-positive spectrum of activity. They are active against multi-resistant cocci, especially Staphylococcus aureus strains. Their physico-chemical and biological properties make them particularly suitable for topical antibacterial use.     

The role of cuticular hydrocarbons in male attraction and repulsion by female Dawson's burrowing bee, Amegilla dawsoni

Cuticular hydrocarbons (CHCs) are long-chain fatty acids and their derivatives that protect insects from desiccation. They can also be important semiochemicals in insect reproduction. We used behavioural and chemical assays to examine the potential role of CHCs in sexual communication in a solitary burrowing bee, Amegilla dawsoni. Washing CHC blends from the cuticle of emerging virgin females made them unattractive to mate-searching males. Returning the CHC blends restored their attractiveness. Nesting females were unattractive to mate-searching males, whether they were washed or not. Chemical analysis identified significant differences between male and female CHC blends and between virgin female and nesting female blends. Some of these differences were due to specific compounds. Loss of attractiveness is unlikely to be due to antiaphrodisiac compounds delivered by males, because male-specific compounds were not found on nesting females, and because recently mated females with intact CHC blends were attractive to searching males. Nesting females could not be made attractive to searching males by removing their CHC blends. Adding virgin female CHC blends tended to improve attractiveness but the effect was weak, suggesting that some form of volatile compound may also be involved in signalling unreceptivity.     

Binding of sperm proacrosin/beta-acrosin to zona pellucida glycoproteins is sulfate and stereodependent. Synthesis of a novel fertilization inhibitor

Specific binding of spermatozoa to the zona pellucida that surrounds mammalian eggs is a key step in the fertilization process. However, the sperm proteins that recognise zona pellucida receptors remain contentious despite longstanding research efforts to identify them. Here we present evidence that proacrosin, a tissue-specific protein found within the acrosomal vesicle of all mammalian spermatozoa, is a multifunctional protein that mediates binding of acrosome-reacted spermatozoa to zona glycoproteins via a stereospecific polysulfate recognition mechanism. Using sulfated versus non-sulfated forms of chemically defined compounds in binding assays employing native proteins in their normal cellular location or conjugated to FluoSpheres, we have attempted to identify the sulfation "code" required for recognition. Results show that protein conformation is important for specificity and that at least 2 sulfate groups are required to cross-link spatially separated docking sites on proacrosin. The consistently most effective inhibitory compounds were suramin and quercetin-3beta-d-glucoside sulfate. The results support our hypothesis that proacrosin is one of several proteins in the acrosomal matrix that retain acrosome reacted spermatozoa on the zona surface prior to penetration. They also establish, as a proof-of-principle, the feasibility of synthesising sulfated compounds of high specificity as antifertility agents for human or animal use.     

Tricyclic quinoxalines as potent kinase inhibitors of PDGFR kinase,Flt3 and Kit

Here we report on novel quinoxalines as highly potent and selective inhibitors of the type III receptor tyrosine kinases PDGFR, FLT3, and KIT. These compounds, tricyclic quinoxalines, were generated in order to improve bioavailability over the highly hydrophobic bicyclic quinoxalines. Four of the highly active compounds were characterized in detail and are shown to inhibit PDGFR kinase activity of the isolated receptor as well as in intact cells in the sub-micromolar concentration range. We show that the most active inhibitor (compound 13, AGL 2043) is approximately 15-20 times more potent than its isomer (compound 14, AGL 2044). We therefore compared the three dimensional structures of the two compounds by X-ray crystallography. These compounds are also highly effective in blocking the kinase activity of FLT3, KIT, and the oncogenic protein Tel-PDGFR in intact cells. These compounds are potent inhibitors of the proliferation of pig heart smooth muscle cells. They fully arrest the growth of these cells and the effect is fully reversible. The chemical, biochemical and cellular properties of these compounds as well as the solubility properties make them suitable for development as anti-restenosis and anti-cancer agents.