ORCID Profile
0000-0002-4932-2030
Current Organisation
University of Sydney
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Analytical Chemistry | Organic Chemical Synthesis | Analytical Spectrometry | Biologically Active Molecules
Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Physical Sciences | Expanding Knowledge in the Biological Sciences |
Publisher: Future Science Ltd
Date: 06-2016
Abstract: Since its discovery in 2008, New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have disseminated globally, facilitated predominantly by gut colonization and the spread of plasmids carrying the bla NDM-1 gene. With few effective antibiotics against NDM-1 producers, and resistance developing to those which remain, there is an urgent need to develop new treatments. To date, most drug design in this area has been focused on developing an NDM-1 inhibitor and has been aided by the wealth of structural and mechanistic information available from high resolution x-ray crystallography and molecular modeling. This review aims to summarize current knowledge regarding the detection of NDM-1 producers, the mechanism of action of NDM-1 and to highlight recent attempts toward the development of clinically useful inhibitors.
Publisher: American Chemical Society (ACS)
Date: 30-05-2012
DOI: 10.1021/JP210803M
Publisher: MDPI AG
Date: 18-10-2022
DOI: 10.3390/MOLECULES27206993
Abstract: Multi-drug resistance is increasing in the pathogenic bacterium S. pneumoniae, which is mainly responsible for meningitis and community-acquired pneumonia (CAP), highlighting the need for new anti-pneumococcal agents. We have identified a potential anti-pneumococcal agent, enol 3, which acts by hindering the cell ision process by perturbing Z-ring dynamics inside the cell. Enol 3 was also shown to inhibit FtsZ polymerization and induce its aggregation in vitro but does not affect the activity of tubulin and alkaline phosphatase. Docking studies show that 3 binds near the T7 loop, which is the catalytic site of FtsZ. Similar effects on Z-ring and FtsZ assembly were observed in B. subtilis, indicating that 3 could be a broad-spectrum anti-bacterial agent useful in targeting Gram-positive bacteria. In conclusion, compound 3 shows strong anti-pneumococcal activity, prompting further pre-clinical studies to explore its potential.
Publisher: Elsevier BV
Date: 2004
Publisher: Elsevier BV
Date: 09-1999
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1RA08389A
Abstract: In this study, the 1:1 cocrystal of theophylline and malonic acid originally engineered by Trask undergoes charge density analysis to rationalise the chemical change process seen throughout crystallisation.
Publisher: Wiley
Date: 29-05-2012
Publisher: MDPI AG
Date: 30-09-2019
DOI: 10.3390/MOLECULES24193550
Abstract: Selective detection of β-alanyl aminopeptidase (BAP)-producing Pseudomonas aeruginosa, Serratia marcescens, and Burkholderia cepacia was achieved by employing the blue-to-yellow fluorescent transition of a BAP-specific enzyme substrate, 3-hydroxy-2-(p-dimethylaminophenyl)flavone derivative, incorporating a self-immolative linker to β-alanine. Upon cellular uptake and accumulation of the substrate by viable bacterial colonies, blue fluorescence was generated, while hydrolysis of the N-terminal peptide bond by BAP resulted in the elimination of the self-immolative linker and the restoration of the original fluorescence of the flavone derivative.
Publisher: Georg Thieme Verlag KG
Date: 05-2008
Publisher: American Chemical Society (ACS)
Date: 13-12-2018
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.BMC.2015.11.013
Abstract: The three peroxisome proliferator-activated receptor (PPAR) isoforms PPARα, PPARγ and PPARδ, play central roles in lipid metabolism and glucose homeostasis. Dual PPARα/γ agonists, which stimulate both PPARα and PPARγ isoforms to similar extents, are gaining popularity as it is believed that they are able to ameliorate the unwanted side effects of selective PPARα and PPARγ agonists and may also be used to treat dyslipidemia and type 2 diabetes mellitus simultaneously. In this study, virtual screening of natural product libraries, using both structure-based and ligand-based drug discovery approaches, identified ten potential dual PPARα/γ agonist lead compounds (9-13 and 16-20). In vitro assays confirmed these compounds to show no statistically significant toxicity to cells, with the exception of compound 12 which inhibited cell growth to 74.5%±3.5 and 54.1%±3.7 at 50μM and 100μM, respectively. In support of their potential as dual PPARα/γ agonists, all ten compounds upregulated the expression of cholesterol transporters ABCA1 and ABCG1 in THP-1 macrophages, with indoline derivative 16 producing the greatest elevation (2.3-fold 3.3-fold, respectively). Furthermore, comparable to the activity of established PPARα and PPARγ agonists, compound 16 stimulated triacylglycerol accumulation during 3T3-L1 adipocyte differentiation as well as fatty acid β-oxidation in HuH7 hepatocytes.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.EJMECH.2015.12.027
Abstract: To overcome the major disadvantages of cysteamine, the only registered treatment for the rare genetic disease cystinosis, nine prodrugs of γ-glutamyl-cysteamine (4) were synthesized for evaluation. Esterification of the thiol conferred oxidative stability, while sufficient lipophilicity for oral bioavailability was achieved by acylation of the α-carboxyl group of γ-glutamyl-cysteamine (4). Low cytotoxicity was observed in cultured HaCaT keratinocytes using the MTT assay, with EC50 values higher than or similar to that of cysteamine. Successful uptake of the esterified prodrugs and the subsequent release of cysteamine into cultured human proximal tubule epithelial cells were demonstrated using CMQT derivatisation and HPLC with UV detection. These prodrugs show potential as novel delivery vehicles of cysteamine to improve the treatment of the genetic disorder nephropathic cystinosis.
Publisher: American Chemical Society (ACS)
Date: 23-03-2012
DOI: 10.1021/JP2108076
Abstract: The experimental electron density distribution (EDD) in 8-hydroxyquinoline cocrystallized with salicylic acid, 1, has been determined from a multipole refinement of high-resolution X-ray diffraction data collected at 100 K. The experimental EDD is compared with theoretical densities resulting from high-level ab initio and BHandH calculations using Atoms in Molecules theory. 1 crystallizes in the triclinic crystal system, and the asymmetric unit consists of a neutral salicylic acid molecule, a salicylate anion, and an 8-hydroxyquinolinium cation exhibiting a number of inter- and intramolecular hydrogen bonds and π-π interactions. Topological analysis reveals that π-π interactions are of the "closed-shell" type, characterized by rather low and flat charge density. In general, the agreement of the topological values (ρ(bcp) and ∇(2)ρ(bcp)) between experiment and theory is good, with mean differences of 0.010 e Å(-3) and 0.036 e Å(-5), respectively. The energetics of the π-π interactions have been estimated, and excellent agreement is observed between the relative energy and the strength of π-stacking derived from the Espinosa approach, with an average difference of only 4.4 kJ mol(-1).
Publisher: Elsevier BV
Date: 02-2010
Publisher: Elsevier BV
Date: 09-1994
Publisher: Elsevier BV
Date: 07-2001
Publisher: Elsevier BV
Date: 05-1998
Publisher: Elsevier BV
Date: 1987
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9RA03118A
Abstract: The WHO global action plan on antimicrobial resistance outlines the need for new diagnostic tools. Point-of-care testing for bacterial infections would enable clinically meaningful interventions using methods that are rapid, low-cost, easy-to-operate, and portable.
Publisher: Wiley
Date: 11-1994
Publisher: American Chemical Society (ACS)
Date: 11-01-2017
DOI: 10.1021/ACS.BIOCHEM.6B00879
Abstract: Inhibition of FtsZ assembly has been found to stall bacterial cell ision. Here, we report the identification of a potent carbocyclic curcumin analogue (2d) that inhibits Bacillus subtilis 168 cell proliferation by targeting the assembly of FtsZ. 2d also showed potent inhibitory activity (minimum inhibitory concentrations of 2-4 mg/L) against several clinically important species of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In addition, 2d displayed a significantly reduced inhibitory effect on human cervical cancer cells in comparison to its effect on bacterial cells. Using live cell imaging of GFP-FtsZ by confocal microscopy, 2d was found to rapidly perturb the cytokinetic FtsZ rings in Bacillus subtilis cells. The immunofluorescence imaging of FtsZ also showed that 2d destroyed the Z-ring in bacteria within 5 min. Prolonged treatment with 2d produced filamentous bacteria, but 2d had no detectable effect either on the nucleoids or on the membrane potential of bacteria. 2d inhibited FtsZ assembly in vitro, whereas it had minimal effects on tubulin assembly. Interestingly, 2d strongly enhanced the GTPase activity of FtsZ and reduced the GTPase activity of tubulin. Furthermore, 2d bound to purified FtsZ with a dissociation constant of 4.0 ± 1.1 μM, and the binding of 2d altered the secondary structures of FtsZ. The results together suggested that the non-natural curcumin analogue 2d possesses powerful antibacterial activity against important pathogenic bacteria, and the evidence indicates that 2d inhibits bacterial proliferation by targeting FtsZ.
Publisher: Informa UK Limited
Date: 21-11-2014
DOI: 10.1080/14786419.2013.856908
Abstract: Two new ceramides, (3S,4S,5R)-3-octadecanoylamino-4-hydroxy-5-dodecane-2,3,4,5-tetrahydrofuran (1) and (3S,4S,5R)-3-[(2R)-2-hydroxyhexacosanoylamino]-4-hydroxy-5-[(4E)-dodecane-4-ene]-2,3,4,5-tetrahydrofuran (2), together with eight known compounds, eleutheroside A (3), eleutheroside B (4), eleutheroside E (5), 7-hydroxy-6-methoxy-coumarin (6), 6,7-dimethoxycoumarin (7), 5α,8α-epidioxyergosta-6,22-dien-3-ol (8), stigmasterol (9) and rutin (10), were isolated from the fruit pulp of Acanthopanax senticosus (Rupr. et Maxim) Harms. Their structures were elucidated by means of physicochemical properties and spectroscopic methods (1D, 2D NMR and MS).
Publisher: Elsevier BV
Date: 06-2005
Publisher: Elsevier BV
Date: 04-2007
Publisher: Informa UK Limited
Date: 10-07-2008
DOI: 10.1080/14786410701642466
Abstract: Bryostatin structures share a commonality of a central bryophan ring, but each differs due to two groups (R(1) and R(2)) that are attached to the bryophan ring via ester bonds. This research examines the impact that conditions such as UV light, acidic and basic conditions can have on the bryostatin structure in the presence of octanoic acid and water. Mass spectrometry (MS) measurements suggest that bryostatin can easily rearrange into various structures under natural conditions by reacting with carboxylates that are ubiquitous in nature. A second set of measurements suggest bryostatin can be hydrolyzed by water, a reaction that has significant implications in both medicinal applications and extraction procedures.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2000
DOI: 10.1097/00001813-200003000-00009
Abstract: Gossypol [(2,2'-binaphthalene)-8,8'-dicarboxaldehyde-1,1',6,6',7,7'-hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl] 1a is a naturally occurring compound extracted from the cotton plant and has been extensively studied as an oral male contraceptive. Its favorable toxicity profile, and the more recent demonstration of anti-tumor activity in animals and humans, prompted us to investigate the role of the aldehyde groups in a structure-activity study in cultured tumor cells. Four racemic compounds were evaluated: gossypol 1a, gossypolone 2, the bis Schiff's base of L-phenylalanine methyl ester with gossypol (bis Schiff's base) 1c and apogossypol 1b. The former two compounds both retain the aldehyde functional groups at positions 8 and 8' of the molecule whilst in the latter two compounds the aldehydes are blocked or absent, respectively. In addition, the l- and d-isomers of gossypol 1a, the bis Schiff's base 1c and the half Schiff's base 1d (one aldehyde blocked) were tested. The cell lines studied included melanoma (SK-mel-19), cervix (Sihas), small cell lung (H69) and myelogenous leukemia (K562). Cytotoxicity was measured using the MTT and flow cytometric viability assays. Racemic gossypol 1a and gossypolone 2 induced similar dose-dependent decreases in cell viability in all the cell lines with IC50 values of 23-46 and 28-50 microM, respectively. In contrast, the racemic bis Schiff's base derivative of gossypol 1c and apogossypol 1b showed minimal activity in any cell line up to 50 microM. The l-enantiomer of gossypol 1a was significantly more active than the d-enantiomer (IC50 of 20 versus > 50 microM, respectively). When one aldehyde of either enantiomer was blocked 1d cytoxicity was comparable to the l-enantiomer of gossypol. The data suggest that only one aldehyde group is required for the cytotoxicity of gossypol 1a, irrespective of the stereoconfiguration.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2CP01235A
Abstract: This study investigated and rationalised the fluorescence modulation of 7-hydroxycoumarin in response to changing concentrations of 2-methylimidazole using low-cost quantum mechanical calculations from single crystal X-ray geometries.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2MD00263A
Abstract: Enzymatic drug deactivation is an important contributor to bacterial resistance. Adjuvants which inhibit the β-lactamases help maintain the efficacy of the β-lactams, demonstrating the potential for this strategy for other antibacterial classes.
Publisher: Elsevier BV
Date: 2002
Publisher: Elsevier BV
Date: 03-1998
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 02-04-2020
Publisher: Oxford University Press (OUP)
Date: 09-1998
Publisher: Elsevier BV
Date: 05-1995
Publisher: Elsevier BV
Date: 1999
DOI: 10.1016/S0304-3835(98)00302-4
Abstract: The naturally occurring compound, gossypol, has been previously used as a male oral contraceptive, for the treatment of benign gynaecological conditions and cancer patients. Long-term daily dosing with gossypol is associated with minimal side effects and no myelosuppression. Since gossypol exhibits atropisomerism due to the restricted rotation about the 2,2' carbon bond, we have isolated the l- and d-isomers by Schiff's base formation using a chiral amine and regenerated the enantiomers by acid hydrolysis. The enantiomers and the proposed oxidative metabolite, gossypolone, were characterized by HPLC, 1H-NMR and optical rotation. The cytotoxicity was assessed in cell cultures derived from melanoma, lung, breast, cervix, and leukaemia using the MTT viability assay. The cytotoxicity of gossypolone was similar to racemic gossypol in five out of the six cell lines studied. The l-enantiomer of gossypol induced a dose-dependent cell kill in all cell lines with a mean IC50 of 20 microM and was significantly more potent than racemic gossypol, the d-enantiomer of gossypol and gossypolone. In addition, when the leukaemia line was exposed to l-gossypol (0.5-10 microM) over a 4-day period, a schedule-dependent decrease in cell viability was observed. l-Gossypol was also compared with respective drugs used to treat patients with melanoma, lung cancer and leukaemia. The data indicate that l-gossypol was significantly more active than cisplatin, melphalan and dacarbazine in the two melanoma lines, cisplatin and daunorubicin in the lung line and hydroxyurea and busulphan in the leukaemia line. Preliminary studies using one melanoma line showed that the l-isomer induced cell shrinkage, membrane blebbing and DNA fragmentation, characteristics suggestive of apoptotic cell death.
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B716978G
Abstract: Novel 7-N-(beta-alanyl)aminophenoxazin-3-one salts 27a-d have been synthesized and tested as chromogenic substrates for beta-alanyl aminopeptidase, which is present in Pseudomonas aeruginosa, the most common respiratory pathogen in patients with cystic fibrosis. The biological results show that 7-N-(beta-alanyl)amino-1-pentylphenoxazin-3-one trifluoroacetate salt 27a is a chromogenic substrate for this bacterium, with a low degree of diffusion in nutrient media for growing bacterial cultures and a bright red colour, making it easily distinguishable from the agar background.
Publisher: American Chemical Society (ACS)
Date: 12-12-2012
DOI: 10.1021/OL303057A
Abstract: The first total synthesis of the marine natural products Psammaplin C and Tokaradine A is described. Benzylidene rhodanines were utilized as versatile intermediates toward the synthesis of seven brominated marine sponge metabolites through the optimization of protection group strategies. Spermatinamine demonstrated good inhibition of all cancer cell lines tested, in particular the leukemia K562 and colon cancer HT29 cell lines.
Publisher: Elsevier BV
Date: 04-2005
Publisher: Bentham Science Publishers Ltd.
Date: 02-2012
Publisher: Oxford University Press (OUP)
Date: 09-1998
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.BMC.2012.07.048
Abstract: Hit compounds from in silico screening for inhibitors of the EGFR dimerization process were evaluated for their anti-proliferative (CCD-1106 keratinocytes) and anti-oxidant (TBA assay) activity and their effect on EGFR dimerization (BS(3) chemical crosslinking assay). 7-Benzyl-8-{N'-[1-(3-ethoxy-4-hydroxyphenyl)meth-(Z)-ylidene]hydrazino}-1,3-dimethylxanthine 2a (127 μM) leads to 37% inhibition of p-EGFR dimerization in the CCD-1106 cell line and also inhibits phosphorylation of proteins in the MAPK/ERK pathway, ERK 1/2 and p-38. Based on this initial data, 2a was selected for further study and was evaluated for its anti-proliferative activity in a range of keratinocyte (CCD-1106, HaCaT and NHEK) and monocyte (ThP1 and U937) cell lines. Xanthine 2a is pro-apoptotic in HaCaT keratinocytes, as shown by electron microscopy, caspase 3/7, and annexin V-FITC/PI flow cytometric assays. It is significantly less cytotoxic than the established antipsoriatic agent dithranol 14, as determined by MTT and LDH release assays, and thus has potential as a lead compound for the treatment of psoriasis.
Publisher: Elsevier BV
Date: 09-1996
Publisher: American Chemical Society (ACS)
Date: 11-01-2018
Publisher: Royal Society of Chemistry
Date: 2007
Publisher: MDPI AG
Date: 18-01-2018
DOI: 10.3390/CRYST8010046
Publisher: Elsevier BV
Date: 1992
Publisher: American Chemical Society (ACS)
Date: 23-05-2012
DOI: 10.1021/NP300102Z
Abstract: Five purpurealidin-derived marine secondary sponge metabolies have been synthesized through the carbodiimide coupling of an appropriate bromotyrosine unit. The structure elucidations have been confirmed through direct comparison with spectroscopic data of isolated natural products. Aplyzanzine A has been shown to be the most active product against a broad bacterial and fungal screen, demonstrating MIC values 2 to 4 times lower than the other metabolites in this study. Compounds 2, 3, 4a, and 5-7 exhibit a modest inhibition against slow growing mycobacteria (MIC 25-50 μg/mL), including Mycobacterium tuberculosis. iso-Anomoian A and suberedamine B showed antitumor activity in the NCI-DTP60 cell line screen at single-digit micromolar concentrations, with iso-anomoian A inhibiting 53 cell lines. These molecules present novel scaffolds for further optimization.
Publisher: Springer Science and Business Media LLC
Date: 06-2004
Publisher: Elsevier
Date: 1996
Publisher: Royal Society of Chemistry (RSC)
Date: 1987
DOI: 10.1039/C39870001367
Publisher: Elsevier BV
Date: 08-2010
Publisher: MDPI AG
Date: 23-12-2023
DOI: 10.3390/PHARMACEUTICS15010049
Abstract: The drug discovery process is a rocky path that is full of challenges, with the result that very few candidates progress from hit compound to a commercially available product, often due to factors, such as poor binding affinity, off-target effects, or physicochemical properties, such as solubility or stability. This process is further complicated by high research and development costs and time requirements. It is thus important to optimise every step of the process in order to maximise the chances of success. As a result of the recent advancements in computer power and technology, computer-aided drug design (CADD) has become an integral part of modern drug discovery to guide and accelerate the process. In this review, we present an overview of the important CADD methods and applications, such as in silico structure prediction, refinement, modelling and target validation, that are commonly used in this area.
Publisher: International Union of Crystallography (IUCr)
Date: 25-07-2012
DOI: 10.1107/S160053681202750X
Abstract: The title compound, C 21 H 26 N 2 O 5 , was unexpectedly obtained as a by-product in the reaction of ethyl acetoacetate, 4-acetamidobenzaldehyde and urea under microwave irradiation. The dihydropyridine ring assumes a flattened boat conformation. Intermolecular N—H...O and weak C—H...O hydrogen bonding occurs in the crystal.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6CP02690G
Abstract: Experimental charge density analysis of two piroxicam polymorphs has found a redistribution of charge to a non-classical zwitterionic form.
Publisher: Royal Society of Chemistry (RSC)
Date: 1993
DOI: 10.1039/C39930001789
Publisher: Elsevier BV
Date: 09-2013
Publisher: Oxford University Press (OUP)
Date: 02-2002
Abstract: HPLC analysis of the urine of autistic subjects indicated the presence of an unidentified component in greatly increased concentrations. We have reported the isolation of this component by HPLC and its identification. Mass spectrometry, NMR and UV spectroscopy identified the peak as corresponding to indolyl-3-acryloylglycine (IAG, 3), and this has been confirmed by an independent synthesis.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6RA10411H
Abstract: Experimental and theoretical charge density of piroxicam, saccharin and their 1 : 1 co-crystal have been determined using high-resolution X-ray diffraction, multipole refinement and DFT calculations
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.BMCL.2007.11.018
Abstract: The synthesis and initial evaluation of novel chromogenic substrates with potential in the detection and differentiation of cultured bacterial colonies are described. The substrates were readily hydrolysed by specific aminopeptidase activity to release the chromogen, 9-(4'-aminophenyl)-10-methylacridinium salt, which provided a clear visual indication of the presence of the corresponding bacteria.
Publisher: Royal Society of Chemistry (RSC)
Date: 04-10-2001
DOI: 10.1039/B104130B
Publisher: Informa Healthcare
Date: 24-01-2006
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6CS00693K
Abstract: In this tutorial review, the techniques involved in the detection of pathogenic bacteria are described.
Publisher: Elsevier BV
Date: 04-1991
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5CP90018B
Abstract: Correction for ‘Experimental and theoretical charge density distribution in Pigment Yellow 101’ by Jonathan J. Du et al., Phys. Chem. Chem. Phys. , 2015, DOI: 10.1039/c4cp04302b.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.BMC.2005.04.026
Abstract: Gossypol 1, gossypolone 2, and a series of bis 3 and half Schiff's bases 4 of gossypol were synthesised and tested for anti-proliferative and anti-oxidant activity. (-)-Gossypol (-)-1 was the most potent inhibitor of the proliferation of the HPV-16 keratinocyte cell line (using an MTT viability assay) with a GI50 of 4.8 microM. The bis Schiff's base of (-)-gossypol with L-tyrosine ethyl ester (-)-3b was the most potent inhibitor of iron/ascorbate dependent lipid peroxidation (using the thiobarbituric acid test), with an IC50 of 11.7 microM, with (-)-gossypol being the next most potent of the series, with an IC50 of 13.1 microM. The results from these initial assays suggest that gossypol, as either a racemic mixture rac-1, or the in idual atropisomers (-)-1 or (+)-1, has potential for the treatment of psoriasis.
Publisher: American Chemical Society (ACS)
Date: 04-05-2016
DOI: 10.1021/ACS.JMEDCHEM.5B01591
Abstract: A series of novel 8-aminophenoxazin-3-one and 7-aminophenoxazin-3-one chromogens and their corresponding β-alanine derivatives were synthesized and evaluated for their ability to detect β-alanyl aminopeptidase activity in bacteria known to hydrolyze β-alanine derivatized substrates. The results provided insight into the structural requirements for effective visualization of enzymatic activity and the mechanism of formation of phenoxazinon-3-ones. 8-Aminophenoxazin-3-one substrates 23c, 23d, and 23e were prepared in good to high overall yield and were selective for β-alanyl aminopeptidase activity in bacteria, producing a lighter agar background coloration facilitating visualization of colored colonies, with variable localization to the colonies, but had lower sensitivities for the detection of Pseudomonas aeruginosa in comparison to the analogous 7-aminophenoxazin-3-one substrates. The synthetic methodology employed here allows the preparation of a range of substrates for evaluation and the establishment of structure-activity relationships. For ex le, the 2-pentyl substituted aminophenoxazin-3-one 22b performed with analogous sensitivity to the corresponding 1-pentyl-7-aminophenoxazin-3-one substrate 1 used commercially, highlighting that the position of the pentyl substituent can be varied while maintaining detection sensitivity.
Publisher: Informa UK Limited
Date: 10-10-2010
DOI: 10.1080/14786419.2010.485304
Abstract: A new triterpenoid, 3,4-seco-lupane-20(29)-ene-3,28-dioic acid, together with three known lignans, (-)-schisandrin B, (-)-sesamin and (-)-syringaresinol, was isolated from the pulp of Acanthopanax senticosus (Rupr. et Maxim) Harms. Their structures were elucidated by means of physicochemical properties and spectroscopic methods (1D, 2D-NMR and MS).
Publisher: Future Science Ltd
Date: 06-2016
Abstract: Filamenting temperature-sensitive mutant Z (FtsZ), an essential cell ision protein in bacteria, has recently emerged as an important and exploitable antibacterial target. Cytokinesis in bacteria is regulated by the assembly dynamics of this protein, which is ubiquitously present in eubacteria. The perturbation of FtsZ assembly has been found to have a deleterious effect on the cytokinetic machinery and, in turn, upon cell survival. FtsZ is highly conserved among prokaryotes, offering the possibility of broad-spectrum antibacterial agents, while its limited sequence homology with tubulin (an essential protein in eukaryotic mitosis) offers the possibility of selective toxicity. This review aims to summarize current knowledge regarding the mechanism of action of FtsZ, and to highlight existing attempts toward the development of clinically useful inhibitors.
Publisher: Elsevier BV
Date: 10-2004
Publisher: American Chemical Society (ACS)
Date: 26-02-2018
Abstract: Experimental charge density distribution studies, complemented by quantum mechanical theoretical calculations, of a host-guest system composed of a macrocycle (1) and barbital (2) in a 1:1 ratio (3) have been carried out via high-resolution single-crystal X-ray diffraction. The data were modeled using the conventional multipole model of electron density according to the Hansen-Coppens formalism. The asymmetric unit of macrocycle 1 contained an intraannular ethanol molecule and an extraannular acetonitrile molecule, and the asymmetric unit of 3 also contained an intraannular ethanol molecule. Visual comparison of the conformations of the macrocyclic ring shows the rotation by 180° of an amide bond attributed to competitive hydrogen bonding. It was found that the intraannular and extraannular molecules inside were orientated to maximize the number of hydrogen bonds present, with the presence of barbital in 3 resulting in the greatest stabilization. Hydrogen bonds ranging in strength from 4 to 70 kJ mol
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2OB06986E
Abstract: Several novel fluorogenic N-aminoacylnaphthyridine substrates were synthesized in good yield and tested for their ability to detect pathogenic bacteria in agar-based cell culture. Simple 2-N-(β-alanyl)amino-5,7-dialkylnaphthyridine substrates were selectively hydrolysed by β-alanylaminopeptidase expressing bacteria, but were subject to diffusion in the agar medium. Diffusion was reduced in the 2-N-(β-alanyl)amino-7-alkylnaphthyridine substrates with longer alkyl chains, but inhibition of growth was increased. 2-N-(β-Alanyl)amino-7-octylnaphthyridine inhibited the growth of all species tested, except for strains resistant to colistin olymyxin, providing a rationale for the development of substrates for the selective detection of drug resistant species in clinical s les.
Publisher: Elsevier BV
Date: 04-1995
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.BMC.2012.11.040
Abstract: Twenty three dual PPARα and γ molecules of natural product origin, previously reported by our group, were further investigated for pan PPAR transactivation against PPARδ. The in vitro cell toxicity profile, as well as, in silico study of the most active molecules within this new class of pan PPAR agonists are also described. 3',5' Dimethoxy-7 hydroxyisoflavone 6, Ψ-baptigenin 7, 4' fluoro-7 hydroxyisoflavone 8, and 3' methoxy-7 hydroxyisoflavone 9 were identified as the most potent molecules studied within the set compared to the commercially available pan PPAR agonist, bezafibrate 1. These novel active molecules may thus be useful as future leads in PPAR-related disorders, including type II diabetes mellitus and metabolic syndrome.
Publisher: Elsevier BV
Date: 02-2016
Publisher: Elsevier BV
Date: 06-2014
Publisher: International Union of Crystallography (IUCr)
Date: 02-07-2011
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6RA12875K
Abstract: The fluorogenic self-immolative substrates 8 are specifically hydrolyzed by β-alanyl aminopeptidase, resulting in a 1,6-elimination and the release of the highly fluorescent hydroxycoumarins 6 .
Publisher: Oxford University Press (OUP)
Date: 10-01-2013
DOI: 10.1111/JPHP.12019
Abstract: Dithranol, one of the most successful topical agents for the treatment of psoriasis, has been shown to exert its therapeutic effect by inducing keratinocyte apoptosis. To gain further insights into dithranol-induced apoptotic events in vitro, a detailed investigation of its time- and dose-dependent effects has been performed through the evaluation of selected apoptotic markers, using a human keratinocyte cell line (HaCaT) as a model. The time- and dose-dependent effects of dithranol on a human keratinocyte cell line (HaCaT) were investigated through the evaluation of a series of apoptotic markers morphological changes (electron microscopy), phosphatidylserine externalisation (flow cytometry), and caspase-3/7 activation. The dithranol-induced apoptotic cascade was found to follow a well-defined dose and time-course, with the concentration and the period of exposure to the drug acting as the two major factors influencing the events and nature of cell death. The earliest apoptotic event detected was caspase activation (after 6 h), followed by the occurrence of phosphatidylserine externalisation (after 9 h) and subsequently the morphological characteristics associated with early and late stage apoptosis/necrosis (after 12 h). This study has elucidated the dose- and time-response effects of dithranol-induced apoptosis in human keratinocytes in vitro.
Publisher: Springer Science and Business Media LLC
Date: 2008
DOI: 10.2478/S11696-008-0025-Z
Abstract: A series of 2-pyrazolines was prepared in a reaction of quinolinylchalcones with phenyl hydrazine under both conventional and microwave-induced heating. Structures of the synthesized compounds were characterized by spectroscopic data and CHN analyses. All prepared compounds were tested for antimicrobial activity against bacterial strains, viz. Staphylococcus aureus, Salmonella typhii, Escherichia coli, and Shigella dysentery. Almost all synthesized compounds have shown antimicrobial activity however, compounds with a chloro group as a substituent have been found to be more effective.
Publisher: Bentham Science Publishers Ltd.
Date: 2011
DOI: 10.2174/138955711793564088
Abstract: A number of studies have identified differential kavalactone activity against a variety of molecular targets, including P-glycoprotein (Pgp), platelet monoamine oxidase (MAO-B), transcription factor binding domains, pregnane X (PXR) and GABA receptors, and cytochrome P450 and cyclo-oxygenase (COX) enzymes. The molecular structure of the kavalactones possesses a pharmacophore for several of these targets. In most cases, conformational stability is more significant than the substituents present. The analysis of these pharmacophores provides important insights for future medicinal chemistry-based approaches to kavalactone-type drugs.
Publisher: American Chemical Society (ACS)
Date: 03-11-2021
Abstract: The charge density distribution in a novel cocrystal (1) complex of 1,3-dimethylxanthine (theophylline) and propanedioic acid (malonic acid) has been determined. The molecules crystallize in the triclinic, centrosymmetric space group
Publisher: Mary Ann Liebert Inc
Date: 06-2010
Abstract: Established treatments for psoriasis are generally based on antiproliferative, anti-inflammatory, or differentiation-modifying activity, or a combination of these effects. New agents for the treatment of psoriasis could be identified by high-throughput screening (HTS) of large compound libraries using keratinocyte proliferation models. Although several new proliferation assays have been developed, the radioactive [(3)H]-thymidine incorporation assay is still considered to be the gold standard for the evaluation of keratinocyte proliferation in vitro. In this study, we compare a number of simple, and reliable, colorimetric (MTT, NRU, SRB, and CVS), and fluorimetric (CAM and AB) methods with the [(3)H]-thymidine incorporation assay for the measurement of keratinocyte proliferation in the exponential growth phase in 96-well formats. The concentrations that induced 50% growth inhibition (GI(50)) were determined by each assay for the established antipsoriatics, dithranol, and methotrexate. Strong correlations were observed between the percentage growth inhibitions determined by the radioactive and the colorimetric assays, with no significant differences (P > 0.05) between their GI(50) values. The colorimetric assays are thus suitable alternatives to the radioactive assay for quantifying keratinocyte growth inhibition. We have also validated the use of the HaCaT cell line as a representative of the hyperproliferative psoriatic epidermis, in the preclinical screening of experimental anti-psoriatic agents.
Publisher: American Chemical Society (ACS)
Date: 19-07-2021
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2018
End Date: 04-2019
Amount: $744,100.00
Funder: Australian Research Council
View Funded Activity