ORCID Profile
0000-0002-4548-6433
Current Organisation
Griffith University Griffith Health
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Proteins and Peptides | Organic Chemistry | Organic Chemical Synthesis | Biologically Active Molecules
Expanding Knowledge in the Chemical Sciences | Cancer and Related Disorders |
Publisher: CSIRO Publishing
Date: 2008
DOI: 10.1071/CH08193
Abstract: Methanesulfonic acid has been found to be a highly effective catalyst for a convenient and one-pot synthesis of 2-substituted benzoxazoles by the reaction of 2-aminophenol with acid chlorides, generated in situ from carboxylic acids. Aryl, heteroaryl, and arylalkyl carboxylic acids provided excellent yields of the corresponding benzoxazoles. The reaction conditions were compatible with various substituents such as chloro, bromo, nitro, methoxy, cyclopentyloxy, phenoxy, thiophenoxy, and conjugated double bonds. Benzoxazole formation was found to be general with respect to substituted 2-aminophenols.
Publisher: American Chemical Society (ACS)
Date: 31-10-2019
DOI: 10.1021/ACS.JMEDCHEM.9B01668
Abstract: Pathological hyperphosphorylation of tau and subsequent aggregation to form neurofibrillary tangles (NFTs) is closely related to progression of neurodegenerative diseases such as Alzheimer's disease (AD) and progressive supranuclear palsy. A recent study showed that MK-8719 (
Publisher: Oxford University Press (OUP)
Date: 03-09-2015
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.BIOORG.2019.103389
Abstract: Numerous post-translational modifications (PTMs) of the Parkinson's disease (PD) associated α-synuclein (α-syn) protein have been recognised to play critical roles in disease aetiology. Indeed, dysregulated phosphorylation and proteolysis are thought to modulate α-syn aggregation and disease progression. Among the PTMs, enzymatic glycosylation with N-acetylglucosamine (GlcNAc) onto the protein's hydroxylated amino acid residues is reported to deliver protective effects against its pathogenic processing. This modification has been reported to alter its pathogenic self-assembly. As such, manipulation of the protein's O-GlcNAcylation status has been proposed to offer a PD therapeutic route. However, targeting upstream cellular processes can lead to mechanism-based toxicity as the enzymes governing O-GlcNAc cycling modify thousands of acceptor substrates. Small glycopeptides that couple the protective effects of O-GlcNAc with the selectivity of recognition sequences may prove useful tools to modulate protein aggregation. Here we discuss efforts to probe the effects of various O-GlcNAc modified peptides on wild-type α-synuclein aggregation.
Publisher: CSIRO Publishing
Date: 2017
DOI: 10.1071/CH17201
Abstract: An efficient synthesis of the O-linked glycosylamino acid Fmoc–l-Ser((Ac)3–β-d-GlcNAc)-OH building block is described. The utility of the method was demonstrated with direct solid-phase O-glycosylation of the hydroxyl group on the amino acid (Ser) side chain of a human α-A crystallin-derived peptide (AIPVSREEK) in nearly quantitative glycosylation yield.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.EJPHAR.2018.09.034
Abstract: This review demonstrates the importance of uncovering the mechanisms that underlie chemotherapy-induced neuroinflammation. It builds upon the well-established connection between chemotherapeutic-agents and neurotoxicity along with widespread peripheral toxicities. This article summarises the major studies which have linked chemotherapy-induced neurodegeneration with direct evidence of neuroinflammation. Cancer and chemotherapy-related adverse effects impact a large proportion of the population. A better understanding of the link between chemotherapy, neurotoxicity and specifically the mechanisms of neuroinflammation, will allow the development of strategies to improve the management of side effects, and overall to reduce the burden on cancer patients receiving chemotherapy. This review has developed a summary schematic of the relationship between different chemotherapeutic agents and inflammatory markers within the central nervous system and links this correlation with some major ailments associated with chemotherapy use.
Publisher: Georg Thieme Verlag KG
Date: 2005
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C1OB06043K
Abstract: 1-Methylimidazole exhibits an unusually high efficiency in promoting the reaction of aryl methyl ketones with DMF-DMA to form (2E)-1-aryl-3-dimethylamino-2-propenones which lacks correlation between the catalytic efficiency and the basicity of 1-methylimidazole in comparison to other amines. An unprecedented supramolecular domino catalysis rationalises the lack of correlation between the catalytic efficiency and basicity of the amines. The supramolecular assemblies have been characterized by mass-spectrometric ion fishing. The time-dependent increase/decrease in the concentration (ion current) of the supramolecular species consolidated the mechanism.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Wiley
Date: 09-2004
Publisher: Georg Thieme Verlag KG
Date: 08-2006
Publisher: Elsevier BV
Date: 03-2013
Publisher: Elsevier BV
Date: 2021
Publisher: Georg Thieme Verlag KG
Date: 2004
Publisher: American Chemical Society (ACS)
Date: 15-04-2019
DOI: 10.1021/ACSCHEMNEURO.9B00143
Abstract: Post-translational modifications (PTMs) of proteins are becoming the focus of intense research due to their implications in a broad spectrum of neurodegenerative diseases. Various PTMs have been identified to alter the toxic profiles of proteins which play critical roles in disease etiology. In Alzheimer's disease (AD), dysregulated phosphorylation is reported to promote pathogenic processing of the microtubule-associated tau protein. Among the PTMs, the enzymatic addition of N-acetyl-d-glucosamine (GlcNAc) residues to Ser/Thr residues is reported to deliver protective effects against the pathogenic processing of both amyloid precursor protein (APP) and tau. Modification of tau with as few as one single O-GlcNAc residue inhibits its toxic self-assembly. This modification also has the same effect on the assembly of the Parkinson's disease (PD) associated α-synuclein (ASyn) protein. In fact, O-GlcNAcylation ( O-linked GlcNAc modification) affects the processing of numerous proteins implicated in AD, PD, amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) in a similar manner. As such, manipulation of a protein's O-GlcNAcylation status has been proposed to offer therapeutic routes toward addressing multiple neurodegenerative pathologies. Here we review the various effects that O-GlcNAc modification, and its modulated expression, have on pathogenically significant proteins involved in neurodegenerative disease.
Publisher: Informa UK Limited
Date: 08-09-2021
Publisher: Elsevier BV
Date: 07-2021
Publisher: Wiley
Date: 23-10-2020
Publisher: Georg Thieme Verlag KG
Date: 20-07-2005
Publisher: Royal Society of Chemistry (RSC)
Date: 2004
DOI: 10.1039/B400588K
Abstract: Silica gel (60-120 mesh) efficiently catalyses the opening of epoxide rings by amines at rt under solvent-free conditions providing an easy method for the synthesis of 2-amino alcohols. Aromatic and aliphatic amines react with cyclohexene oxide with exclusive formation of the trans-2-aryl/alkylaminocyclohexanols in high yields. A complementary regioselectivity is exhibited by aromatic and aliphatic amines during the reaction with styrene oxide. The epoxide ring of non-styrenoidal unsymmetrical alkene oxide undergoes selective nucleophilic attack at the sterically less hindered carbon by aniline.
Publisher: Wiley
Date: 10-07-2019
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7RA12950E
Abstract: Menaquinone is essential in electron transport and ATP generation in all Gram-positive, and anaerobically respiring Gram-negative bacteria. Inhibition of menaquinone production at different steps of the biosynthesis pathway has shown promising novel antibacterial action.
Publisher: American Chemical Society (ACS)
Date: 18-06-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1MA00569C
Abstract: Perovskite halides hold great potential for high-energy radiation detection. Recent advancements in detecting alpha-, beta-, X-, and gamma-rays by perovskite halides are reviewed and an outlook on the device performance optimization is provided.
Publisher: Bentham Science Publishers Ltd.
Date: 14-09-2023
Publisher: Bentham Science Publishers Ltd.
Date: 04-04-2018
DOI: 10.2174/1570163814666170531115452
Abstract: Human Immunodeficiency Virus Type 1 Integrase or HIV-1 integrase (IN) is a 288 amino acid protein that incorporates the retrotranscribed viral DNA into the host chromosomal DNA. Over the past 30 years, large number of derivatives have been evaluated for their inhibitory potential against IN. There is vast literature available which need to be collated to help scientists plan the future drug design. This review discusses the reports of past 25 years on analogs of quinoline, coumarin and other related heterocycles, which exhibit low micromolar inhibitory potency against IN.
Publisher: Springer Science and Business Media LLC
Date: 04-10-2020
Publisher: MDPI
Date: 07-08-2019
Publisher: SAGE Publications
Date: 27-08-2020
Abstract: Reduction in sensitivity in terms of cytotoxicity is responsible for therapy failure in patients undergoing chemotherapy with first-line anticancer drug molecules. A plethora of literature evidence points out that increased O-linked β- N-acetylglucosamine transferase (OGT) enzyme level/hyper- O-GlcNAcylation has direct implications in development of cancer and interferes with clinical outcomes of chemotherapy via interaction with oncogenic factors. The aim of this research was to evaluate the combination approach of anticancer drugs with an OGT inhibitor (OSMI-1) as an alternative way to resolve issues in the treatment of prostate cancer and assess the benefits offered by this approach. Effect of combination of doxorubicin and docetaxel with OSMI-1 on drug-induced cell death and synergism/antagonism was investigated using resazurin assay. Reduction in OGT enzyme level was evaluated using ELISA kit. Caspase-3/7 fluorescence assay was performed to detect apoptosis induction in PC-3 cells after treatment with the combinations of doxorubicin and OGT inhibitor to further understand the mechanism of cell death by concomitant treatment. Studies reveal that combination approach is indeed effective in terms of reducing the half-maximum growth inhibition value of doxorubicin when concomitantly treated with OSMI-1 and has synergistic effect in prostate cancer cells. PC-3 cells exhibited elevated levels of OGT enzyme in comparison to WPMY-1, and OSMI-1 has potential to inhibit OGT enzyme significantly. Data show that OSMI-1 alone and in combination with doxorubicin reduces OGT enzyme level significantly accompanied by increased apoptosis in prostate cancer cells. Combination of doxorubicin with OSMI-1 reduced the elevated OGT level which led to a drastic increase in sensitivity of PC-3 cells toward doxorubicin in comparison to doxorubicin alone. This finding provides important insight regarding alternative treatment strategies for effective management of cancer.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.EJMECH.2019.01.071
Abstract: The present status of antibiotic resistant requires an urgent invention of novel agents that act on clinically unexplored antibacterial targets. The enzyme MraY (phospho-MurNAc-pentapeptide translocase), essential for bacterial cell wall synthesis, fulfils this criterion as it has not been explored as a target in a clinical context. Specifically, the enzyme is involved in the lipid-linked cycle of peptidoglycan biosynthesis and is reportedly targeted by naturally-occurring nucleoside antibiotics. The antimicrobial 'caprazamycin' class of nucleoside antibiotics targets Mycobacterium tuberculosis and clinically relevant Gram-negative bacteria such as Pseudomonas aeruginosa besides various drug resistant strains and is therefore an eligible starting point for the development of novel agents. In this review, we aim to summarise the structure-activity relationships of the natural, semi-synthetic as well as synthetic analogues of nucleoside antibiotic caprazamycins. This review highlights caprazamycins as promising lead structures for development of potent and selective antimicrobial agents that target MraY, the bacterial enzyme involved in the first membrane-dependent step in bacterial peptidoglycan assembly.
Publisher: Elsevier BV
Date: 04-2004
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2OB25627D
Abstract: Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the expanded active site cavity of influenza virus sialidases with an open 150-loop, currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4, N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing evidence of the relative 150-loop flexibility of these sialidases. In a complex with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150-cavity while the central ring and the remaining substituents bind the active site as seen for the unsubstituted template. This new class of inhibitors, which can 'trap' the open 150-loop form of the sialidase, should prove useful as probes of 150-loop flexibility.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8RA90011F
Abstract: Correction for ‘Menaquinone biosynthesis inhibition: a review of advancements toward a new antibiotic mechanism’ by M. Boersch et al. , RSC Adv. , 2018, 8 , 5099–5105.
Publisher: Elsevier BV
Date: 10-2004
Publisher: Elsevier BV
Date: 09-2005
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.BMC.2013.05.054
Abstract: Novel 3,4-disubstituted-Neu5Ac2en derivatives have been synthesised to probe the open 150-loop conformation of influenza virus sialidases. Both equatorially and axially (epi) substituted C4 amino and guanidino 3-(p-tolyl)allyl-Neu5Ac2en derivatives were prepared, via the 4-epi-hydroxy derivative. The equatorially-substituted 4-amino derivative showed low micromolar inhibition of both group-1 (pdm09 H1N1) and group-2 (pdm57 H2N2) sialidases, and provides the first in vitro evidence that a group-2 sialidase may exhibit 150-loop flexibility.
Publisher: Elsevier BV
Date: 10-2004
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2CC02100E
Abstract: A conjugate vaccine comprising a mycobacterial peptide antigen from the 6 kDa early secretory antigenic target (ESAT6) and a macrophage inducible C-type lectin (Mincle) signalling trehalose dibehenate (TDB) glycolipid adjuvant is described.
Publisher: Wiley
Date: 12-06-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B710414F
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.BBAGEN.2019.04.002
Abstract: A reversible post-translational protein modification which involves addition of N-acetylglucosamine (GlcNAc) onto hydroxyl groups of serine and/or threonine residues which is known as O-GlcNAcylation, has emerged as a potent competitor of phosphorylation. This glycosyltransfer reaction is catalyzed by the enzyme O-linked β-N-acetylglucosamine transferase (OGT). This enzyme uses uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the end product of hexosamine biosynthetic pathway, to modify numerous nuclear and cytosolic proteins. O-GlcNAcylation influences cancer cell metabolism in such a way that hyper-O-GlcNAcylation is considered as a prominent trait of many cancers, and is proposed as a major factor enabling cancer cell proliferation and progression. Growing evidence supports a connection between O-GlcNAcylation and major oncogenic factors, including for ex le, c-MYC, HIF-1α, and NF-κB. A comprehensive study of the roles of O-GlcNAc modification of oncogenic factors is warranted as a thorough understanding may help drive advances in cancer diagnosis and therapy. The focus of this article is to highlight the interplay between oncogenic factors and O-GlcNAcylation along with OGT in cancer cell proliferation and survival. The prospects for OGT inhibitors will also be discussed.
Publisher: Wiley
Date: 22-03-2018
Publisher: American Chemical Society (ACS)
Date: 21-05-2018
DOI: 10.1021/ACSCHEMNEURO.8B00185
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for 60-80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted toward the aggregation of the tau protein as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed. Diagnosis of AD has shifted from measuring late stage senile plaques to early stage biomarkers, amyloid-β and tau monomers and oligomeric assemblies. Synthetic peptides and some derivative structures are being explored for use as theranostic tools as they possess the capacity both to bind the biomarkers and to inhibit their pathological self-assembly. Several studies have demonstrated that O-linked glycoside addition can significantly alter amyloid aggregation kinetics. Furthermore, natural O-glycosylation of amyloid-forming proteins, including amyloid precursor protein (APP), tau, and α-synuclein, promotes alternative nonamyloidogenic processing pathways. As such, glycopeptides and related peptidomimetics are being investigated within the AD field. Here we review advancements made in the last 5 years, as well as the arrival of sugar-based derivatives.
Publisher: MDPI AG
Date: 05-07-2016
Abstract: Radiation therapy is a highly utilized therapy in the treatment of malignancies with up to 60% of cancer patients receiving radiation therapy as a part of their treatment regimen. Radiation therapy does, however, cause a wide range of adverse effects that can be severe and cause permanent damage to the patient. In an attempt to minimize these effects, a small number of compounds have been identified and are in use clinically for the prevention and treatment of radiation associated toxicities. Furthermore, there are a number of emerging therapies being developed for use as agents that protect against radiation-induced toxicities. The aim of this review was to evaluate and summarise the evidence that exists for both the known radioprotectant agents and the agents that show promise as future radioprotectant agents.
Start Date: 01-2014
End Date: 12-2018
Amount: $395,220.00
Funder: Australian Research Council
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