Synthesis,characterization and in vitro biological evaluation of some novel 1,3,5-triazine–Schiff base conjugates as potential antimycobacterial agents

A series of some novel 1,3,5-triazine–Schiff base conjugates (1–32) have been synthesized and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using Alamar Blue assay and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. Compounds 4 (4-Methoxy-6-methyl-N-(3,4,5-trimethoxybenzylidene)-1,3,5-triazin-2-amine), 11 (4-Methoxy-6-methyl-N-(2-hydroxy-3-bromo-5-chloro-benzylidene)-1,3,5-triazin-2-amine) and 24 (4-Methoxy-6-methyl-N-(1-(2,5-dihydroxyphenyl)ethylidene)-1,3,5-triazin-2-amine) exhibited a significant activity at 3.125, 6.25 and 6.25 μg/mL, respectively, when compared with the antitubercular drugs such as ethambutol (3.125 μg/mL), pyrazinamide (6.25 μg/mL) and streptomycin (6.25 μg/mL) and it could be a potential starting point to develop new lead compounds in the fight against Mycobacterium tuberculosis H37Rv.     

Forthcoming Meetings 1993

The purpose of this review is to bring together the different approaches for studying the oxidation of low density lipoproteins and try to identify some critical factors which will permit greater comparability between laboratories. These issues are discussed both in terms of the variety of exogenous mediators of oxidation applied (transition metal ions, haem proteins, azo initiators, peroxynitrite, cells etc.) and their raisons d'etre, as well as the methodologies (formation of conjugated dienes, hydroperoxides, decomposition products of lipid peroxidation, altered surface charge, macrophage uptake) applicable to the different stages of the oxidation and the factors underlying their accurate execution and interpretation.     

Hierarchical sampling for metastable conformers determines biomolecular recognition: the case of malectin and diglucosylated N-glycan interactions

Structural information over the entire course of binding interactions based on the analyses of energy landscapes is described, which provides a framework to understand the events involved during biomolecular recognition. Conformational dynamics of malectin’s exquisite selectivity for diglucosylated N-glycan (Dig-N-glycan), a highly flexible oligosaccharide comprising of numerous dihedral torsion angles, are described as an example. For this purpose, a novel approach based on hierarchical sampling for acquiring metastable molecular conformations constituting low-energy minima for understanding the structural features involved in a biologic recognition is proposed. For this purpose, four variants of principal component analysis were employed recursively in both Cartesian space and dihedral angles space that are characterized by free energy landscapes to select the most stable conformational substates. Subsequently, k-means clustering algorithm was implemented for geometric separation of the major native state to acquire a final ensemble of metastable conformers. A comparison of malectin complexes was then performed to characterize their conformational properties. Analyses of stereochemical metrics and other concerted binding events revealed surface complementarity, cooperative and bidentate hydrogen bonds, water-mediated hydrogen bonds, carbohydrate–aromatic interactions including CH–π and stacking interactions involved in this recognition. Additionally, a striking structural transition from loop to β-strands in malectin CRD upon specific binding to Dig-N-glycan is observed. The interplay of the above-mentioned binding events in malectin and Dig-N-glycan supports an extended conformational selection model as the underlying binding mechanism.     

Visitor Perceptions of Nature Conservation at Helsinki Zoo

These days zoos often claim that their main objective is the promotion of nature conservation and that they strive to educate their visitors about animals and nature conservation. But how do zoo visitors themselves perceive this emphasis on conservation education? In order to determine how Helsinki Zoo visitors perceive nature conservation during their visit, we undertook a qualitative analysis of 75 structured situational interviews and five autoethnographical visits. Our results show that there was only a limited understanding of nature conservation among the zoo visitors. Their perception follows the typical framing of nature conservation in zoos: conservation projects that embrace captive breeding, in-situ conservation collaboration, and the reintroduction of those species. Moreover, in the Helsinki Zoo case these perceptions may have been influenced by the fact that the zoo did not give concrete advice on how the visitors themselves can contribute to conservation, except in terms of donating money. Framing nature conservation in such ways distances it from visitors’ everyday lives.     

Study on biomolecules in extractives of Camellia oleifera fruit shell by GC–MS

This study aims to present an integrated process that can be used to produce biomedical and biological active components from the fruit shell of Camellia oleifera Abel. Through the Foss method, Aldehyde, acid compounds, acyl and alcohol compounds account for 22.7, 15.93, 0.24 and 61.13% of the extractives which were extracted from Camellia oleifera fruit shell by methanol solvents. Furfural, Pyrazole-4-carboxaldehyde, 1-methyl- and 5-Hydroxymethylfurfural account for 4.74, 1.22 and 58.78% of the extractives which were extracted from the fruit shell of Camellia oleifera Abel by ethanol solvents. Aldehyde, acid and amine compounds account for 5.01, 56.18 and 7.20% of the extractives which were extracted from the fruit shell of Camellia oleifera Abel by ethyl acetate solvents. The extractives of fresh flesh of bayberry were rich in rare drug, biomedical and biological activities.     

Alveolar mimics with periodic strain and its effect on the cell layer formation

We report on the development of a new model of alveolar air–tissue interface on a chip. The model consists of an array of suspended hexagonal monolayers of gelatin nanofibers supported by microframes and a microfluidic device for the patch integration. The suspended monolayers are deformed to a central displacement of 40–80 µm at the air–liquid interface by application of air pressure in the range of 200–1,000 Pa. With respect to the diameter of the monolayers, that is, 500 µm, this displacement corresponds to a linear strain of 2–10% in agreement with the physiological strain range in the lung alveoli. The culture of A549 cells on the monolayers for an incubation time of 1–3 days showed viability in the model. We exerted a periodic strain of 5% at a frequency of 0.2 Hz for 1 hr to the cells. We found that the cells were strongly coupled to the nanofibers, but the strain reduced the coupling and induced remodeling of the actin cytoskeleton, which led to a better tissue formation. Our model can serve as a versatile tool in lung investigations such as in inhalation toxicology and therapy.     

Liposome-mediated labeling of adrenocorticotropin fragments parallels their biological activity

To test our hypothesis that specific interactions of ACTH peptides with model lipid membranes reflect the biological importance of similar interactions on target cells, we investigated the liposome-mediated labeling of ACTH fragments with the extremely hydrophobic photolabel, 3-trifluoromethyl-3-(m-[125I]iodophenyl)diazirine. Correlations were found between the labeling rates and the agonistic and antagonistic potencies of the peptides for in vitro steroidogenesis and inhibition of a synaptosomal protein kinase. A model for the cross-reactivity between ACTH and opioid peptides is discussed.     

Secondary Metabolites as Plant Traits: Current Assessment and Future Perspectives

Referee: Dr. Peter B. Kaufman, Dept. of Biology, University of Michigan, Ann Arbor, MI 48109-1048 Traditionally, secondary metabolites in plants have been investigated by phytochemists. Originally classified as waste products, these compounds more recently have been investigated extensively by ecologists and pharmacologists, and many complex biological functions have been discovered. Secondary metabolites occur nearly in all living organisms, within bacteria as well as in mammals, and are especially prominent in those organisms lacking an immune system. Functions of plant secondary metabolites comprise attractants, such as color pigments and scents, repellents such as antifeedants against insects and mammals, or toxins that affect growth and development of animal and microbial predators. Conversely, insects can employ plant-synthesized compounds to their own advantage, such as signals for feeding and oviposition and location of prey. Microbes also use secondary metabolites as carbon sources, and bacteria utilize them for quorum-sensing, an aspect recently discovered. Despite the diversity of recognized functions, the biochemical processes underlying these interactions are few. Primarily, they relate to the ability of these small molecules to bind to receptor regions of various proteins such as keys into locks. This review attempts a summary of current knowledge of secondary plant metabolism with focus on history of discovery, development of analytical techniques, theories of origin and function, signal pathways, biosynthesis, and assessment of biological activities. Outlined is current utilization by, and future perspectives in, different disciplines, such as chemosystematics, chemical ecology, and agricultural biotechnology. Examples illustrate the strong potential of research in secondary metabolism, particularly in comparison to more established disciplines such as developmental biology and physiology.     

Tadpole-like Conformations of Huntingtin Exon 1 Are Characterized by Conformational Heterogeneity that Persists regardless of Polyglutamine Length

Soluble huntingtin exon 1 (Httex1) with expanded polyglutamine (polyQ) engenders neurotoxicity in Huntington's disease. To uncover the physical basis of this toxicity, we performed structural studies of soluble Httex1 for wild-type and mutant polyQ lengths. Nuclear magnetic resonance experiments show evidence for conformational rigidity across the polyQ region. In contrast, hydrogen–deuterium exchange shows absence of backbone amide protection, suggesting negligible persistence of hydrogen bonds. The seemingly conflicting results are explained by all-atom simulations, which show that Httex1 adopts tadpole-like structures with a globular head encompassing the N-terminal amphipathic and polyQ regions and the tail encompassing the C-terminal proline-rich region. The surface area of the globular domain increases monotonically with polyQ length. This stimulates sharp increases in gain-of-function interactions in cells for expanded polyQ, and one of these interactions is with the stress-granule protein Fus. Our results highlight plausible connections between Httex1 structure and routes to neurotoxicity.