ORCID Profile
0000-0002-5051-4830
Current Organisation
University of Sydney
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Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.EJMECH.2019.07.036
Abstract: Activation of the CB
Publisher: American Chemical Society (ACS)
Date: 22-10-2021
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: 20-04-2022
DOI: 10.1021/ACSCHEMNEURO.1C00822
Abstract: Synthetic cannabinoid receptor agonists (SCRAs) are a large and growing class of new psychoactive substances (NPSs). Two recently identified compounds, MEPIRAPIM and 5F-BEPIRAPIM (NNL-2), have not been confirmed as agonists of either cannabinoid receptor subtype but share structural similarities with both SCRAs and a class of T-type calcium channel (Ca
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1MD00242B
Abstract: Synthetic cannabinoid receptor agonists (SCRAs) remain one the most prevalent classes of new psychoactive substances (NPS) worldwide, and ex les are generally poorly characterised at the time of first detection.
Publisher: Frontiers Media SA
Date: 17-09-2021
Abstract: Prostate cancer is the second most prevalent malignancy worldwide. In the early stages, the development of prostate cancer is dependent on androgens. Over time with androgen deprivation therapy, 20% of prostate cancers progress to a castration-resistant form. Novel treatments for prostate cancers are still urgently needed. Erianin is a plant-derived bibenzyl compound. We report herein that erianin exhibits anti-tumor effects in androgen-sensitive and castration-resistant prostate cancer cells through different mechanisms. Erianin induces endoplasmic reticulum stress-associated apoptosis in androgen-sensitive prostate cancer cells. It also triggers pro-survival autophagic responses, as inhibition of autophagy predisposes to apoptosis. In contrast, erianin fails to induce apoptosis in castration-resistant prostate cancer cells. Instead, it results in cell cycle arrest at the M phase. Mechanistically, C16 ceramide dictates differential responses of androgen-sensitive and castration-resistant prostate cancer cells to erianin. Erianin elevates C16 ceramide level in androgen-sensitive but not castration-resistant prostate cancer cells. Overexpression of ceramide synthase 5 that specifically produces C16 ceramide enables erianin to induce apoptosis in castration-resistant prostate cancer cells. Our study provides both experimental evidence and mechanistic data showing that erianin is a potential treatment option for prostate cancers.
Publisher: Oxford University Press (OUP)
Date: 29-05-2018
DOI: 10.1093/JAC/DKY187
Abstract: The prevalence of azole resistance in Aspergillus fumigatus is uncertain in Australia. Azole exposure may select for resistance. We investigated the frequency of azole resistance in a large number of clinical and environmental isolates. A. fumigatus isolates [148 human, 21 animal and 185 environmental strains from air (n = 6) and azole-exposed (n = 64) or azole-naive (n = 115) environments] were screened for azole resistance using the VIPcheck™ system. MICs were determined using the Sensititre™ YeastOne YO10 assay. Sequencing of the Aspergillus cyp51A gene and promoter region was performed for azole-resistant isolates, and cyp51A homology protein modelling undertaken. Non-WT MICs/MICs at the epidemiological cut-off value of one or more azoles were observed for 3/148 (2%) human isolates but not amongst animal, or environmental, isolates. All three isolates grew on at least one azole-supplemented well based on VIPcheck™ screening. For isolates 9 and 32, the itraconazole and posaconazole MICs were 1 mg/L (voriconazole MICs 0.12 mg/L) isolate 129 had itraconazole, posaconazole and voriconazole MICs of >16, 1 and 8 mg/L, respectively. Soil isolates from azole-exposed and azole-naive environments had similar geometric mean MICs of itraconazole, posaconazole and voriconazole (P > 0.05). A G54R mutation was identified in the isolates exhibiting itraconazole and posaconazole resistance, and the TR34/L98H mutation in the pan-azole-resistant isolate. cyp51A modelling predicted that the G54R mutation would prevent binding of itraconazole and posaconazole to the haem complex. Azole resistance is uncommon in Australian clinical and environmental A. fumigatus isolates further surveillance is indicated.
Publisher: MDPI AG
Date: 18-01-2018
DOI: 10.3390/CRYST8010046
Publisher: American Chemical Society (ACS)
Date: 11-04-2022
DOI: 10.1021/ACSCHEMNEURO.2C00034
Abstract: Synthetic cannabinoid receptor agonists (SCRAs) are a erse class of new psychoactive substances (NPS). They commonly comprise
Publisher: Frontiers Media SA
Date: 28-09-2022
DOI: 10.3389/FPSYT.2022.1010501
Abstract: Synthetic cannabinoid receptor agonists (SCRAs) continue to make up a significant portion new psychoactive substances (NPS) detected and seized worldwide. Due to their often potent activation of central cannabinoid receptors in vivo , use of SCRAs can result in severe intoxication, in addition to other adverse health effects. Recent detections of AB-4CN-BUTICA, MMB-4CN-BUTINACA, MDMB-4F-BUTICA and MDMB-4F-BUTINACA mark a continuation in the appearance of SCRAs bearing novel tail substituents. The proactive characterization c aign described here has facilitated the detection of several new SCRAs in toxicological case work. Here we detail the synthesis, characterization, and pharmacological evaluation of recently detected SCRAs, as well as a systematic library of 32 compounds bearing head, tail, and core group combinations likely to appear in future. In vitro radioligand binding assays revealed most compounds showed moderate to high affinity at both CB 1 (p K i = & 5 to 8.89 ± 0.09 M) and CB 2 (p K i = 5.49 ± 0.03 to 9.92 ± 0.09 M) receptors. In vitro functional evaluation using a fluorescence-based membrane potential assay showed that most compounds were sub-micromolar to sub-nanomolar agonists at CB 1 (pEC 50 = & 5 to 9.48 ± 0.14 M) and CB 2 (pEC 50 = 5.92 ± 0.16 to 8.64 ± 0.15 M) receptors. An in silico receptor-ligand docking approach was utilized to rationalize binding trends for CB 2 with respect to the tail substituent, and indicated that rigidity in this region (i.e., 4-cyanobutyl) was detrimental to affinity.
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: 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: 30-12-2020
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: Elsevier BV
Date: 06-2017
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: American Society for Microbiology
Date: 11-2019
DOI: 10.1128/AAC.00632-19
Abstract: The past decade has seen an increase in aspergillosis in humans and animals due to Aspergillus viridinutans species complex members. Azole resistance is common to these infections, carrying a poor prognosis. cyp51A gene mutations are the main cause of acquired azole resistance in Aspergillus fumigatus . This study aimed to determine if the azole-resistant phenotype in A. viridinutans complex members is associated with cyp51A mutations or extrolite profiles.
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: 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: American Chemical Society (ACS)
Date: 19-07-2021
No related grants have been discovered for Felcia Lai.