Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

A series of structurally amphiphilic biscationic norbornanes have been synthesised as rigidified, low molecular weight peptidomimetics of cationic antimicrobial peptides. A variety of charged hydrophilic functionalities were attached to the norbornane scaffold including aminium, guanidinium, imidazolium and pyridinium moieties. Additionally, a range of hydrophobic groups of differing sizes were incorporated through an acetal linkage. The compounds were evaluated for antibacterial activity against both Gram-negative and Gram-positive bacteria. Activity was observed across the series; the most potent of which exhibited an MIC's ≤ 1 μg mL(-1) against Streptococcus pneumoniae, Enterococcus faecalis and several strains of Staphylococcus aureus, including multi-resistant methicillin resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate (VISA) S. aureus.

Norbornane-based peptidomimetics as antibacterial agents

 A library of norbornane-based peptide mimetics have been synthesised and shown to exhibit antibacterial activity against a range of troublesome Gram-positive and Gram-negative bacterial pathogens.

Developing an anion host for lipid A binding and antibacterial activity

New structural amphiphiles 2a and 2b bind the diphosphate lipid A anion and show potential as lead compounds for the development of novel antibacterial agents.

The origin of the antibacterial property of bamboo

Bamboo is an eco-friendly and multifunctional plant. Bamboo clothing has recently entered the textile market with a claim for its antimicrobial properties, but without scientific evidence. In this study, the antibacterial activity of plant extracts from Australian-grown bamboo (Phyllostachys pubescens) is investigated. Bamboo extracts were made using water, dimethyl sulphoxide (DMSO) and dioxane and their antibacterial properties were compared against Gram-negative bacteria, Escherichia coli. It was found that the extract made in 20% DMSO aqueous solution showed weak antibacterial activity, whereas the extract made using 90% dioxane aqueous solution exhibited strong antibacterial activity, even after 20 times dilution. The results indicate that antibacterial agents of P. pubescens are located in lignin, not in hemicellulose or other water-soluble chemical components.

Novel 1,4-substituted-1,2,3-triazoles as antitubercular agents

Tuberculosis (TB) remains a pressing unmet medical need, particularly with the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. Here, a series of 1,4-substituted-1,2,3-triazoles have been synthesized and evaluated as potential antitubercular agents. These compounds were assembled via click chemistry in high crude purity and in moderate to high yield. Of the compounds tested, 12 compounds showed promising antitubercular activity with six possessing minimum inhibitory concentration (MIC) values <10 μg mL^-1, and total selectivity for Mycobacterium tuberculosis (Mtb) growth inhibition. A second set of 21 compounds bearing variations on ring C were synthesized and evaluated. This second library gave an additional six compounds displaying MIC values ≤10 μg mL^-1 and total selectivity for Mtb growth inhibition. These compounds serve as an excellent starting point for further development of antitubercular therapies.

Drug bioactivation, covalent binding to target proteins and toxicity relevance

A number of therapeutic drugs with different structures and mechanisms of action have been reported to undergo metabolic activation by Phase I or Phase II drug-metabolizing enzymes. The bioactivation gives rise to reactive metabolites/intermediates, which readily confer covalent binding to various target proteins by nucleophilic substitution and/or Schiff's base mechanism. These drugs include analgesics (e.g., acetaminophen), antibacterial agents (e.g., sulfonamides and macrolide antibiotics), anticancer drugs (e.g., irinotecan), antiepileptic drugs (e.g., carbamazepine), anti-HIV agents (e.g., ritonavir), antipsychotics (e.g., clozapine), cardiovascular drugs (e.g., procainamide and hydralazine), immunosupressants (e.g., cyclosporine A), inhalational anesthetics (e.g., halothane), nonsteroidal anti-inflammatory drugs (NSAIDSs) (e.g., diclofenac), and steroids and their receptor modulators (e.g., estrogens and tamoxifen). Some herbal and dietary constituents are also bioactivated to reactive metabolites capable of binding covalently and inactivating cytochrome P450s (CYPs). A number of important target proteins of drugs have been identified by mass spectrometric techniques and proteomic approaches. The covalent binding and formation of drug-protein adducts are generally considered to be related to drug toxicity, and selective protein covalent binding by drug metabolites may lead to selective organ toxicity. However, the mechanisms involved in the protein adduct-induced toxicity are largely undefined, although it has been suggested that drug-protein adducts may cause toxicity either through impairing physiological functions of the modified proteins or through immune-mediated mechanisms. In addition, mechanism-based inhibition of CYPs may result in toxic drug-drug interactions. The clinical consequences of drug bioactivation and covalent binding to proteins are unpredictable, depending on many factors that are associated with the administered drugs and patients. Further studies using proteomic and genomic approaches with high throughput capacity are needed to identify the protein targetsof reactive drug metabolites, and to elucidate the structure-activity relationships of drug's covalent binding to proteins and their clinical outcomes.

Synthesis of norbornane bisether antibiotics via silver-mediated alkylation

A small series of norbornane bisether diguanidines have been synthesized and evaluated as antibacterial agents. The key transformation-bisalkylation of norbornane diol 6-was not successful using Williamson methodology but has been accomplished using Ag2O mediated alkylation. Further functionalization to incorporate two guanidinium groups gave rise to a series of structurally rigid cationic amphiphiles; several of which (16d, 16g and 16h) exhibited antibiotic activity. For example, compound 16d was active against a broad range of bacteria including Pseudomonas aeruginosa (MIC = 8 µg/mL), Escherichia coli (MIC = 8 µg/mL) and methicillin-resistant Staphylococcus aureus (MIC = 8 µg/mL).

`Zealotry or nostalgic regret`? women leaders in technical and further education in Australia : agents of change, entrepreneurial educators or corporate citizens?

Education has been restructured in many Western post-industrial nation states during the 1990s. The Australian Technical and Further Education sector (TAFE) has been particularly susceptible to discourses of responsiveness to the market and the new entrepreneuralism. This article explores how women have been repositioned in contradictory and ambiguous ways as the new entrepreneurial middle managers by existing and emergent discourses that circulated in and through TAFE organizations. In turn, it points to how discourses of change management and client responsiveness took on particular readings within specific institutional and professional cultures of the eight Technical and Further Education institutions (TAFEs). At the same time, the restructuring that arose from the corporatization of TAFE, in a highly gendered process, through the twin strategies of marketization and the new managerialism produced new possibilities for individual women educators who moved up into middle management. Yet these individual women were positioned within highly masculinist 'neo-corporate bureaucratic cultures' that co-opted their passion for the capacity of education to make a difference and incorporated these new entrepeneurial work identities.

Accessing database information using mobile agents

Many real-world applications on the Internet require accessing database information and typical technology employed is client/server plus Web (C/S + Web). Although past few years saw many success applications by using this technique, there are still some drawbacks that need to be overcome. One of the drawbacks is that the transaction often fails if the network connection is unstable. Another disadvantage is high bandwidth requirement and latency. This paper argues that mobile agent technology provide an easy way to overcome the shortcomings in CIS + Web in database access on the Internet. A success case study using mobile agents to admit new students to China's institutions is then presented. The mobile agent was created by using IBM's Aglets Software Development Kit (SDK). Based on the experimental results, it is evident that mobile agent technology is well suited for such applications.

Agents and stream data mining: a new perspective

Many organizations struggle with the massive amount of data they collect. Today, data does more than serve as the ingredients for churning out statistical reports. They help support efficient operations in many organizations, and to some extent, data provide the competitive intelligence organizations need to survive in today's economy. Data mining can't always deliver timely and relevant results because data are constantly changing. However, stream-data processing might be more effective, judging by the Matrix project.

Initial value generation for matchmaking in middle agents

One of the major challenges that agents used in open environments must face is that they must be able to find each other. This is because in an open environment, agents might appear and disappear unpredictably. To address this issue, middle agents have been proposed. The performance of middle agents relies heavily on the matchmaking algorithms used. Matchmaking is the process of finding an appropriate provider for a requester through a middle agent. The practical performance of service provider agents has a significant impact on the matchmaking outcomes of middle agents. Thus the track records of agents in accomplishing similar tasks in the past should be taken into account in matchmaking process. Considering that there are no track records available at the launching of an agent system, this paper discusses some ways to provide reasonable initial values for the track  records. With the agents' history and the initial vallies ofthe track records, the performance of matchmaking algorithms can be improved significantly.

An improvement to matchmaking algorithms for middle agents

A question frequently asked in multi-agent systems (MASs) concerns the efficient search for suitable agents to solve a specific problem. To answer this question, different types of middle agents are usually employed. The performance of middle agents relies heavily on the matchmaking algorithms used. Matchmaking is the process of finding an appropriate provider for a requester through a middle agent. There has been substantial work on matchmaking in different kinds of middle agents. To our knowledge, almost all currently used matchmaking algorithms missed one point when doing matchmaking -- the matchmaking is only based on the advertised capabilities of provider agents. The actual performance of provider agents in accomplishing delegated tasks is not considered at all. This results in the inaccuracy of the matchmaking outcomes as well as the random selection of provider agents with the same advertised capabilities. The quality of service of different service provider agents varies from one agent to another even though they claimed they have the same capabilities. To this end, it is argued that the practical performance of service provider agents has a significant impact on the matchmaking outcomes of middle agents. An improvement to matchmaking algorithms is proposed, which makes the algorithms have the ability to consider the track records of agents in accomplishing delegated tasks. How to represent, accumulate, and use track records as well as how to give initial values for track records in the algorithm are discussed. A prototype is also built to verify the algorithm. Based on the improved algorithm, the matchmaking outcomes are more accurate and reasonable.