Inhibition of nonenzymic lipid peroxidation by benzylisoquinoline alkaloids.

A group of benzylisoquinoline alkaloids, including five simple benzylisoquinolines, three phtalideisoquinolines, six aporphines, three protoberberines, and two benzophenanthridines, have been studied as inhibitors of lipid peroxidation stimulated by Fe2+/cysteine in rat liver microsomal fractions. Protopapaverine, apomorphine, laudanosoline, tetrahydroberberine, isoboldine, bulbocapnine, boldine, anonaine, glaucine, and stepholidine showed antiperoxidative effects, and structure-activity relationships were established. In simple benzylisoquinolines, the presence of phenolic hydroxyls or similar reactive groups is necessary for inhibition of peroxidation, while in aporphines and protoberberines nonhydroxylated compounds can exert antiperoxidative effects. The phtalideisoquinolines and benzophenanthridines tested were inactive.     

Distribution of Benzylisoquinolines in Magnoliidae and Other Taxa

Based on the analysis of benzylisoquinoline alkaloids of 323 samples in 11 families, 50 genera and 181 species of the Chinese flora discussed in this paper are the biogenesis, evolution, distribution pattern and botanical sources as well as the pharmacological action of this specific category of alkaloids. Benzylisoquinoline alkaloids are found mainly in Magnoliidae, in which aporphines, bisbenzylisoquinolines and protoberberines are the three major types of the alkaloids. More specifically, aporphines appeare more concentrated in primitive woody plants such as the Annonaceae, while bisbenzylisoquinolines are especially common in the Menispermaceae, Thalictrum (the Ranunculaceae) and Berberis (the Berberidaceae). As to protoberberines, the quaternary ones occur mainly in the families Ranunculaceae and Berberidaceae, whereas the tertiary ones mainly in the relatively advanced families Menispermaceae and Papaveraceae within Magnoliidae. As a whole, a general rule can be drawn that the simpler the chemical structure of the benzylisoquinolines is, the more widely they are distributed in primitive groups; more specific ones only have a limited distribution in more advanced groups or even within one family or one to several genera. This general pattern of distribution of benzylisoquinoline alkaloids in plants may be of value as a taxonomic criterion for plant systematics. Furthermore, this group of alkaloids covers the gamut of pharmacologic responses, such as the antibacterial effect and the effect to cardiovascular and nervous systems, and consequently the correlation between benzylisoquinoline alkaloids and their pharmacologicactivities within Magnoliidae may worthily be applied for the finding of new drugs.     

Neolignans from the seeds of Prunus tomentosa (Rosaceae) and their chemotaxonomic interest

The role of neolignans in the chemotaxonomy of the genus Prunus has long been neglected. In this study, two new dihydrobenzofuran neolignans tomentosanans A (12) and B (14), together with 15 known neolignans, were isolated from the seeds of Prunus tomentosa. This is the first report on the occurrence of compounds 1–12, 14, 15 and 17 in the genus Prunus. The biosynthetic pathways of these neolignans are also summarized. Together, these neolignans represent a phytochemical fingerprint for P. tomentosa, which may be used for identification of Prunus species.     

Absolute configuration of the benzofuranoid neolignans

The benzofuranoid neolignans, classified into structurally homogeneous groups by constitution and ORD curves, have had their relative configurations es     

Comparative Scaling of Humeral Cross-Sections of Felids and Canids Using Radiographic Images

The cortical thickness of long bones can be an effective indicator of locomotor modes and other stresses encountered by bone. Felids and canids are two carnivoran families that have similar levels of phylogenetic diversity and overlap in body size, but differ in their locomotor habits. Many canids and felids are cursorial, but felids also climb more frequently than canids. Felids also display a secondary use for their forelimbs not observed in any canids: they use their forelimbs to grasp and subdue prey. Large felids use their forelimbs much more extensively to subdue prey than do large canids and, therefore, should have proportionately greater forces applied to their forelimbs. This study uses a non-invasive radiographic approach to examine the differences in cortical thickness in the humerus between the Felidae and Canidae, as well as between size groups within these two families. Results show few significant differences between the two families, with a slight trend toward more positive allometry in the felids. Overall, radiographic measurements were found to be better predictors of body mass than either prey killing behavior or locomotor mode in these two carnivoran families. One canid that demonstrated exceptionally high cortical area was the bush dog, Speothos venaticus. The rarely observed bush dog has been postulated to swim and dig regularly, and it may be that the thickened cortical bone reflects these behaviors.     

Amenyunnaosides A–C,Three New Neolignans Isolated from Amentotaxus yunnanensis and Their Anti-inflammatory Activities

Phytochemical study on the leaves of Amentotaxus yunnanensis led to the isolation of seventeen phenolic compounds including sixteen neolignans and lignans, and one flavone glycoside. Three among the isolates were previously unreported neolignans and named as amenyunnaosides A–C, respectively. Their structures were elucidated by extensive analyses of HR-ESI-MS, 1D and 2D NMR, and ECD spectra. The isolated neolignans potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC₅₀ values ranging from 11.05 to 44.07 μM, compared to that of the positive control compound, dexamethasone, IC₅₀ value of 16.93 μM. Additionally, amenyunnaoside A dose-dependently reduced production of IL-6 and COX-2 but did not effect to that of TNF-α at concentrations of 0.8, 4, and 20 μM.     

Different numbers of maternal and paternal siblings of cystic fibrosis patients

Summary When 458 parents of children suffering from cystic fibrosis (CF) from all over the German Democratic Republic were interviewed to determine the number of their siblings, it was found that the maternal families had a total of 1369 children and the paternal, 1220. While the fathers of CF patients tended to originate from families with one or two children, more mothers than fathers came from families with three to twelve children (P=0.01). The average number of children in the maternal families was 2.99; in the paternal families, only 2.66. To rule out any methodological errors, sibs of mothers and fathers of various control groups were studied. We found that the number of siblings in these groups was balanced. The differences in our findings are probably due to CF heterozygosity. The underlying mechanism is unknown.     

Chemosystematics of Aniba

A taxonomic subdivision of the genus Aniba (Lauraceae) which comprises 41 recognized species is, for the major part, compatible with a chemical subdivision of the genus which can be made on the basis of the mutually exclusive presence of neolignans vs benzophenones, pyrones and flavonoids. While the presence of neolignans is considered a primitive character of the genus Aniba, the occurrence of pyrones and biosynthetically related compounds is regarded as an advanced character. The chemistry of two closely allied species, of which one produces neolignans, the other pyrones plus an allylphenol, gives a clue for the understanding of the chemical evolution within this genus, for which a unified biosynthetic scheme is presented.     

Chemosystematic implications of benzyltetrahydroisoquinolines in Aniba

The presence of simple benzyltetrahydroisoquinolines in Aniba species, known for their varied phenylpropanoid chemistry, is reported. Since other genera in the Lauraceae contain, in contrast, quite elaborate alkaloidal types, a regulating mechanism may exist by which phenylalanine is channelled either into phenylpropanoids or into benzylisoquinolines. This mechanism is evoked in order to rationalize chemical evolution in the Magnoliidae.     

Neolignans from Virola carinata fruit

The fruits of Virola carinata contain the lignans (?)-cubebin, (?)-hinokinin and (+)-asarinin, besides four neolignans of the β-aryloxy-arylpropane type and two neolignans of the benzodioxane (eusiderin) type.     

The first record of neolignans from the marine phanerogam Posidonia oceanica

Chemical analysis of the secondary metabolites of Posidonia oceanica rhizomes led to the identification of several compounds. In particular, two neolignans, co-occurring with related metabolites previously described from the plant kingdom, have been isolated and characterised by spectroscopic methods. To the best of our knowledge, this is the first report of neolignans from a marine phanerogam.     

An (R)-specific N-methyltransferase involved in human morphine biosynthesis

The biosynthesis of morphine, a stereochemically complex alkaloid, has been shown to occur in plants and animals. A search in the human genome for methyltransferases capable of catalyzing the N-methylation of benzylisoquinoline alkaloids, as biosynthetic precursors of morphine, yielded two enzymes, PNMT (EC 2.1.1.28) and NMT (EC 2.1.1.49). Introduction of an N-terminal poly-histidine tag enabled purification of both proteins by immobilized metal affinity chromatography. Recombinant PNMT and NMT were characterized for their catalytic activity towards four benzylisoquinolines: tetrahydropapaveroline (THP), 6-O-methyl-THP, 4′-O-methyl-THP and norreticuline. Human PNMT accepted none of the offered alkaloids and was only active with its established substrate, phenylethanolamine. The second enzyme, human NMT, converted all four benzylisoquinolines, however, with a strict preference for (R)-configured morphine precursors. Determination of kinetic parameters of NMT for the four (R)-configured benzylisoquinoline alkaloids by LC–MS/MS revealed (R)-norreticuline to be the best substrate with an even higher catalytic activity as compared to the previously reported natural substrate tryptamine. In addition, isolation of the morphine precursor salutaridine from urine of mice injected (i.p.) with (R)-THP provides new evidence that the initial steps of morphine biosynthesis in mammals occur stereochemically and sequentially differently than in plants and suggests an involvement of the herein characterized (R)-specific NMT.     

Studies on the Chemical Constituents of Piper hancei Maxim III

In continuation with our work on the neolignans of Piper hancei, two new neolignans, hancinone B (Ⅰa) and hancinone C (Ⅱ), with a known compound, crotepoxide, were isolated. The structures of la and Ⅱ have been identified by spectroscopic and chemical analysis.     

Structure-function relationships in microbial exopolysaccharides

Sufficient well-characterized microbial exopolysaccharides are now available to permit extensive studies on the relationship between their chemical structure and their physical attributes. This is seen even in homopolysaccharides with relatively simple structures but is more marked when greater differences in structure exist, as are found in several heteropolysaccharides. The specific and sometimes unique properties have, in the case of several of these polymers, provided a range of commercial applications. The existence of "families" of structurally related polysaccharides also indicates the specific role played by certain structures and substituents; the characteristics of several of these microbial polysaccharide families will be discussed here. Thus, microbial exopolysaccharides frequently carry acyl groups which may profoundly affect their interactive properties although these groups often have relatively little effect on solution viscosity. Xanthan with or without acylation shows marked differences in synergistic gelling with plant gluco- and galacto-mannans, although the polysaccharides with different acylation patterns show similar viscosity. Similarly "gelrite" from the bacterium originally designated as Auromonas (Pseudomonas)elodea is of greater potential value after deacetylation, when it provides a valuable gelling agent, than it is as a viscosifier in the natural acylated form. The Klebsiella type 54 polysaccharide only forms gels when it, too, has been chemically deacetylated to give a structure equivalent to the Enterobacter XM6 polymer. Both these polysaccharides form gels due to the enhanced interaction with cations following deacylation and to the conformation adopted after removal of the acyl groups. Recent work in our laboratory suggests that deacetylation of certain bacterial alginates also significantly increases ion binding by these polysaccharides, making them more similar in their properties to algal alginates even although the alginates from some Pseudomonas species lack poly-L-guluronic acid sequences. The existence within families of polysaccharides of types in which monosaccharides are altered within a specific structure, or with varying side-chains, also gives an indication of the way in which such substituents affect the physical properties of the polymers in aqueous solution.     

Furanosidase superfamily: search of homologues

The furanosidase superfamily contains GH32, GH43, GH62, GH68, GH117, DUF377, and DUF1861 families of glycoside hydrolases and their homologues. Catalytic domains of these families have five-bladed beta-propeller tertiary structure. Iterative screening of the protein database allowed to support their relationship as well as evolutionary connections with domains from GH33 and GH93 families of glycoside hydrolases. The latter two have structure of the six-bladed beta-propeller. Among revealed homologues we found 441 unclassified proteins. These proteins are combined into 39 groups based on homology: FURAN1-FURAN39. FURAN8 and FURAN36 can be considered as separate subfamilies within GH43 and GH32 families of glycoside hydrolases, respectively. The remaining 37 groups are new families of hypothetical glycoside hydrolases.     

Molecular systematics of the bark lice infraorder Caeciliusetae (Insecta: Psocodea)

The phylogenetic relationships of bark lice and parasitic lice (Insecta: Psocodea) have been studied in a number of recent molecular phylogenetic analyses based on DNA sequences. Many of these studies have focused on the position of parasitic lice within the free‐living bark lice. However, fewer such studies have examined the relationships among major groups of free‐living bark lice and their implications for classification. In this study we focus on the infraorder Caeciliusetae, a large group of bark lice (?1000 species) within the suborder Psocomorpha. Using sequences of two mitochondrial and two nuclear genes, we estimated the phylogeny for relationships among the five recognized families within the infraorder Caeciliusetae. Based on the results, the sister‐group relationship and respective monophyly of Stenopsocidae and Dasydemellidae is strongly supported. Monophyly of the larger families Amphipsocidae and Caeciliusidae was not supported, although the causes of this were the placement of two distinct subfamilies (Paracaeciliinae and Calocaeciliinae). The monophyly of Asiopsocidae could not be tested because it was sampled only by one species. Based on these results and consideration of morphological characters, we propose a new classification for Caeciliusetae, recognizing six families: Amphipsocidae, Stenopsocidae, Dasydemellidae, Asiopsocidae, Paracaeciliidae and Caeciliusidae. We expect that this new classification will stabilize the higher‐level taxonomy of this group and help to identify groups in need of further work among these insects.     

CFTR Haplotype Analysis Reveals Genetic Heterogeneity in the Etiology of Congenital Bilateral Aplasia of the Vas Deferens

Congenital bilateral aplasia of the vas deferens (CBAVD) was suggested to be a mild form of cystic fibrosis (CF). Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in males with CBAVD revealed that in some males CBAVD is caused by two defective CFTR alleles. The genetic basis of CBAVD in the other males and its association with CF remained unclear. We undertook this study to test the hypothesis of commonality of CBAVD and CF by haplotype analysis, in the CFTR locus, of males suffering from CBAVD and of their families. According to the hypothesis of commonality of CBAVD and CF, two brothers with CBAVD are expected to carry the same two CFTR alleles, while their fertile brothers are expected to carry at least one different allele. Eleven families were studied, of which two families, with unidentified CFTR mutations, did not support this hypothesis. In these families two brothers with CBAVD inherited different CFTR alleles. Their fertile brothers inherited the same CFTR alleles as their brothers with CBAVD. These results provide evidence for genetic heterogeneity in CBAVD. Though in some families CBAVD is associated with two CFTR mutations, we suggest that in others it is caused by other mechanisms, such as mutations at other loci or homozygosity or heterozygosity for partially penetrant CFTR mutations.     

Comparative analysis of stilbene and benzofuran neolignan derivatives as acetylcholinesterase inhibitors with neuroprotective and anti-inflammatory activities

Stilbenes and benzofuran neolignans are important groups of plant phenolics therefore they play a significant role in plants and human health. The objective of this study was to investigate the structure-activity relationships of naturally occurring stilbene and benzofuran neolignan derivatives as acetylcholinesterase inhibitors. A series of these compounds were prepared and assessed for their inhibition on acetylcholinesterase activity. δ-Viniferin, pterostilbene trans-dehydrodimer, pallidol, grossamide, and boehmenan exerted acetylcholinesterase inhibitory potential. The several oligomeric compounds protected against cell damage resulting from t-BHP exposure and inhibited lipopolysaccharide/interferon-gamma (LPS/IFNγ)-induced NO production in vitro. Our findings highlight the great potential of pterostilbene trans-dehydrodimer, pallidol, and boehmenan as multifunctional nutraceuticals for management of neurodegenerative diseases.