A5014227303- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Neuroendocrine regulation and behavior
- Chemical synthesis and alkaloids
- Crystallography and molecular interactions
- Microbial Natural Products and Biosynthesis
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Lichen and fungal ecology
- Asymmetric Synthesis and Catalysis
- Neuroscience of respiration and sleep
- Synthesis and Biological Evaluation
- Organic Chemistry Cycloaddition Reactions
- Adenosine and Purinergic Signaling
- Pharmacological Receptor Mechanisms and Effects
- S100 Proteins and Annexins
- Click Chemistry and Applications
- Porphyrin and Phthalocyanine Chemistry
- Cyclopropane Reaction Mechanisms
- Nicotinic Acetylcholine Receptors Study
- Ubiquitin and proteasome pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Catalytic C–H Functionalization Methods
- Neuropeptides and Animal Physiology
- Cannabis and Cannabinoid Research
University of Canberra
2023-2025
UNSW Sydney
2023-2025
UNSW Canberra
2023-2025
Australian National University
2011-2024
Canberra (United Kingdom)
2020-2023
The University of Sydney
2013-2022
ETH Zurich
2015-2017
Instituto de Estudos Avançados da Universidade de São Paulo
2014
Biased agonism at G protein-coupled receptors describes the phenomenon whereby some drugs can activate downstream signaling activities to relative exclusion of others. Descriptions biased focusing on differential engagement proteins versus β-arrestins are commonly limited by small response windows obtained in pathways that not amplified or less effectively coupled receptor engagement, such as β-arrestin recruitment. At μ-opioid (MOR), protein-biased ligands have been proposed induce...
Cubane is a highly strained saturated hydrocarbon system that has historically been of interest in theoretical organic chemistry. More recently it become molecule for biological applications due to its inherent stability and limited toxicity. Of greater significance the ability potentially functionalize cubane at each carbon atoms, providing complex biologically active molecules with unique spatial arrangements probing sites. These characteristics have led an increased use pharmaceutically...
at the Aβ plaques locations, while NeuN labelling revealed an age-dependent decrease in hippocampal neuron number both genotypes.Behavioural assessment using novel object recognition task that WT & TgF344-AD animals discriminated from familiar 3 m and 6 of age.However, low levels exploration observed genotypes later time-points resulted neither genotype successfully completing task.Deficits social interaction were only animals.By vivo MRS, we showed a neuronal marker N-acetyl-aspartate...
There is current interest in oxytocin (OT) as a possible therapeutic psychiatric disorders. However, the usefulness of OT may be constrained by peripheral autonomic effects, which involve an action at both and vasopressin V1A receptors. Here, we characterized cardiovascular thermoregulatory effects OT, (AVP) non-peptide receptor agonist WAY 267,464 rats, assessed relative involvement receptors these effects.Biotelemetry freely moving male Wistar rats was used to examine body temperature...
Over the past decades, positron emission tomography (PET) imaging has become an increasingly useful research modality in field of multiple sclerosis (MS) research, as PET can visualise molecular processes, such neuroinflammation, vivo. The second generation radioligand [18F]DPA714 binds with high affinity to 18-kDa translocator-protein (TSPO), which is mainly expressed on activated microglia. aim this proof concept study was evaluate vivo marker neuroinflammation primary and secondary...
Over the past 20 years, neuroinflammation (NI) has increasingly been recognised as having an important role in many neurodegenerative diseases, including Alzheimer's disease. As such, being able to image NI non-invasively patients is critical monitor pathological processes and potential therapies targeting neuroinflammation. The translocator protein (TSPO) proven a reliable biomarker for positron emission tomography (PET) imaging. However, if TSPO imaging acute conditions such stroke...
The racemic modification of the Aspidosperma alkaloid limaspermidine (1) has been prepared in ten steps including one involving a Raney-cobalt-mediated tandem reductive cyclization nitrile 8 to give tetracyclic system 9b. Compound (±)-1 converted over two into (±)-1-acetylaspidoalbidine [(±)-13].
The pathophysiology of post-treatment Lyme disease syndrome (PTLDS) may be linked to overactive immunity including aberrant activity the brain's resident immune cells, microglia. Here we used [11C]DPA-713 and positron emission tomography quantify 18 kDa translocator protein, a marker activated microglia or reactive astrocytes, in brains patients with symptoms any duration compared healthy controls. Genotyping for TSPO rs6971 polymorphism was completed, individuals rare, low affinity binding...
The DYRK family contains kinases that are up-regulated in malignancy and control several cancer hallmarks. To assess the anticancer potential of inhibitors targeting kinases, we developed a series novel based on 7-azaindole scaffold. All compounds were tested for their ability to inhibit DYRK1A, DYRK1B, DYRK2, structurally related CLK1. library was screened efficacy established stem cell-like glioblastoma cell lines. most potent (IC50 ≤ 50 nM) significantly decreased viability, clonogenic...
Usnic acid is a secondary metabolite abundantly found in lichens, for which promising cytotoxic and antitumor potential has been shown. However, knowledge concerning activities of its derivatives limited. Herein, series usnic were synthesized their antiproliferative potency against cancer cells different origin was assessed. Some the compounds more active than acid. Compounds 2a 2b inhibited survival all tested cell lines dose- time-dependent manner. Their IC50 values after 48 h treatment...
Derivatives of usnic acid (UA), a secondary metabolite from lichens, were synthesized to improve its anticancer activity and selectivity. Recently we reported the synthesis an UA isoxazole derivative, named 2b, against cancer cells different origins. Herein, molecular mechanisms underlying efficacy in vivo tested. The viability breast or normal has been tested using MTT assay. Cell organelle morphology was analyzed light, electron fluorescence microscopy. Gene expression evaluated by RNAseq...
The impact of the isoxazole derivative usnic acid, ISOXUS (formerly known as 2b) on cancer and non-cancerous cell metabolism was investigated. significantly reduced utilisation most metabolic substrates that produce NADH or FADH2, mitochondrial electron flow oxygen consumption rate (OCR) in MCF-7 breast cells contrast to HB2 normal epithelial cells. Molecular docking revealed inhibits respiratory chain complex II, which confirmed experimentally. Disturbance resulted increased reactive...
Metastasis is the leading cause of cancer-related death. This multistage process involves contribution from both tumour cells and stroma to release metastatic into circulation. Circulating (CTCs) survive circulatory cytotoxicity, extravasate colonise secondary sites effecting outcome. Reprogramming transcriptomic landscape a hallmark, but detecting underlying master regulators that drive pathological gene expression key challenge, especially in childhood cancer. Here we used whole plus...
Methicillin-resistant Staphylococcus aureus (MRSA) has proven to be an imminent threat public health, intensifying the need for novel therapeutics. Previous evidence suggests that cannabinoids harbour potent antibacterial activity. In this study, a group of previously inaccessible phytocannabinoids and synthetic analogues were examined potential The minimum inhibitory concentrations dynamics bacterial inhibition, determined through resazurin reduction time-kill assays, revealed activity...
The readily accessible enones 8, 17, and 18 undergo 2-fold reductive cyclization reactions upon exposure to hydrogen in the presence of Raney-cobalt thereby afford compounds 11 (72%), 19 (47%), 20 (84%), respectively. These products embody ABCD-ring system associated with title alkaloids, compound can be converted, over four steps 33% yield, into congener 24 incorporating ABCDE-ring Strychnos alkaloids.
Seven-membered rings that contain one or more heteroatoms are interesting motifs for organic synthesis. In addition to their synthetic interest, they play an important role in industrial and pharmaceutical chemistry with generally increased central nervous system activity when flanked by aromatic rings. Herein we report a brief summary of some key methods preparation seven-membered-ring heterocycles how have been applied the synthesis commercially desirable products. We then detail new...
The first comprehensive survey of the application catalyst RANEY® cobalt in chemical synthesis is presented. Its capacity to effect chemoselective reductive cyclisation reactions under mild conditions highlighted.
We report on a series of electron donor-acceptor conjugates incorporating ZnII -porphyrin-based donor and variety non-conjugated rigid linkers connecting to push-pull chromophores as acceptors. The acceptors comprize multicyanobutadienes or extended tetracyanoquinodimethane analogues with first reduction potentials ranging from -1.67 -0.23 V vs. Fc+ /Fc in CH2 Cl2 , which are accessible through final-step cycloaddition-retroelectrocyclization (CA-RE) reaction. Characterization the includes...
Buta-1,3-dienes appended with electron-withdrawing groups (EWGs), derived from the [2 + 2] cycloaddition–retroelectrocyclization (CA–RE) cascade, react (predominately) nitrogen-based nucleophiles affording tetrasubstituted 2-amino-NH-pyrroles in moderate to excellent yields complete regioselectivity. Penta-2,4-dien-1-ones also undergo a similar transformation, providing analogous products and greatly enhancing substitution of pyrrole available. Oxidation pyrrolidinone affords highly colored...