Susan Semple

Antiviral flavonoid from Pterocaulon sphacelatum, an Australian Aboriginal medicine

Publisher: Elsevier BV

Date: 12-1999

DOI: 10.1016/S0378-8741(99)00050-1

Abstract: The antipicornaviral activity of an ethanolic extract of the green aerial parts of the Australian plant Pterocaulon sphacelatum (Labill.) Benth. & Hook. f. ex F. Muell. has been investigated. This plant has been a favoured traditional medicine, used for the treatment of colds by the Australian Aboriginal people. Antiviral activity-guided fractionation of the extract of P. sphacelatum using an inhibition of poliovirus-induced cytopathic effect assay, has yielded the antiviral flavonoid chrysosplenol C (3,7,3'-trimethoxy-5,6,4'-trihydroxyflavone). This compound is a 4'-hydroxy-3-methoxyflavone, one of a group of compounds known to be potent and specific inhibitors of picornaviral replication. These compounds inhibit the replication of rhinoviruses, the most frequent causative agent of the common cold. The coumarin 6,7,8-trimethoxycoumarin was also isolated from the ethanolic extract.

Community pharmacists in Australia: Barriers to information provision on complementary and alternative medicines

Publisher: Springer Science and Business Media LLC

Date: 21-11-2006

DOI: 10.1007/S11096-006-9058-Y

Abstract: To determine, by surveying Australian community pharmacists, the perceived barriers to the provision of information about complementary and alternative medicines (CAMs) and suggestions for overcoming them. Anonymous, self-administered survey sent to a random s le of 701 pharmacists registered in three states of Australia in 2004. Pharmacists' perceived barriers to the provision of information about CAMs. A total of 344 questionnaires were returned by pharmacists (49% response) of which 211 (30%) were currently practising in community pharmacy. Ninety-five percent of surveyed community pharmacists indicated that they personally received enquires about CAMs, with fewer than 15% reporting they were "very confident" in answering queries about safety, interactions or benefits of CAMs. Frequently used CAM information sources were those from manufacturers and distributors, professional newsletters and journals and textbooks. Pharmacists' perceived barriers to the provision of CAM information included a lack of suitable training (most training was informal), deficiencies in available information sources, a lack of managerial support, the need for regulatory changes, consumer beliefs about CAM safety and time constraints due to competing demands in daily practice. Pharmacists proposed improvements to overcome these barriers including improvements to training. There is scope for pharmacy professional organisations and educational institutions to further support pharmacists in their practice through providing information on the best information sources available and training that meets the needs of undergraduate students, pharmacists and other pharmacy staff. There is a need to examine regulatory requirements concerning the provision of product information with CAMs in Australia and to implement mechanisms for increasing consumer awareness of regulatory procedures for these medicines.

PHYTOTHERAPIES USED BY INDIGENOUS POPULATIONS

Publisher: Wiley

Date: 24-04-2015

DOI: 10.1002/9781119006039.CH6

Antibacterial activity of traditional Australian medicinal plants

Publisher: Elsevier BV

Date: 10-2001

DOI: 10.1016/S0378-8741(01)00290-2

Abstract: Fifty-six ethanolic extracts of various parts of 39 plants used in traditional Australian Aboriginal medicine were investigated for their antibacterial activities against four Gram-positive (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus and Streptococcus pyogenes) and four Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhimurium) bacterial species. In a plate-hole diffusion assay, 12 extracts inhibited the growth of one or more of the bacteria, with five extracts showing broad spectrum antibacterial activity against Gram-positive bacteria. B. cereus was the most susceptible bacterium, with all 12 extracts displaying activity against this organism. Extracts from the leaves of Eremophila species (Myoporaceae) were the most active, with Eremophila duttonii exhibiting the greatest activity (against Gram-positive bacteria). The antibacterial effects of E. duttonii were further investigated by time-course growth assays which showed that significant growth inhibition was observed in cultures incubated in the presence of the extract within 1 h for B. cereus, E. faecalis and S. aureus and 2 h for S. pyogenes.

Pharmaceutical care services: A systematic review of published studies, 1990 to 2003, examining effectiveness in improving patient outcomes

Publisher: Oxford University Press (OUP)

Date: 03-2005

DOI: 10.1211/0022357055551

Abstract: To systematically review the evidence for the effect of pharmaceutical care practice on patient outcomes. Community and outpatient setting. Randomised controlled trials (RCTs) published in English between 1990 and 2003 were identified through a systematic literature search. To be included, studies had to assess the effect of a pharmaceutical care intervention, defined as a one-to-one consultation between each patient and a pharmacist with a focus on managing health or resolving drug-related problems, development of a care plan and follow-up. Twenty-two RCTs met the review criteria. Studies targeted general patient populations at risk of drug-related problems, disease-specific target groups or patients with risk factors including hypertension and raised cholesterol. While a number of trials have been undertaken, the variability in the application of endpoints utilised means the evidence for effectiveness of single endpoints apart from quality of life is generally limited to one or two controlled trial results. Collectively, the studies provide evidence that the service improves signs and symptoms for people with asthma, surrogate endpoints such as blood pressure, cholesterol levels and glycosylated haemoglobin and medication use, but do not provide evidence supporting improved health-related quality of life. One study showed an improvement in combined all-cause mortality and non-fatal heart failure-related events in patients with heart failure. Pharmaceutical care services are effective in improving medication use and surrogate endpoints, but improvement in other outcomes is less conclusive. Given that the focus of the service is to resolve medication-related problems, consideration should be given to the use of adverse drug events and resolution of medication-related problems as an outcome measure in future studies.

Characterization of serrulatane diterpenoids in Eremophila phyllopoda subsp. phyllopoda by triple high-resolution α-glucosidase/PTP1B/radical scavenging profiling, NMR spectroscopy, DFT-GIAO NMR, and electronic circular dichroism calculations

Publisher: American Chemical Society (ACS)

Date: 07-03-2023

DOI: 10.1021/ACS.JNATPROD.2C00692

Screening of Australian medicinal plants for antiviral activity

Publisher: Elsevier BV

Date: 03-1998

DOI: 10.1016/S0378-8741(97)00152-9

Abstract: Extracts of 40 different plant species used in the traditional medicine of the Australian Aboriginal people have been investigated for antiviral activity. The extracts have been tested for activity against one DNA virus, human cytomegalovirus (HCMV) and two RNA viruses, Ross River virus (RRV) and poliovirus type 1, at non-cytotoxic concentrations. The most active extracts were the aerial parts of Pterocaulon sphacelatum (Asteraceae) and roots of Dianella longifolia var. grandis (Liliaceae), which inhibited poliovirus at concentrations of 52 and 250 microg/ml, respectively. The extracts of Euphorbia australis (Euphorbiaceae) and Scaevola spinescens (Goodeniaceae) were the most active against HCMV. Extracts of Eremophila latrobei subsp. glabra (Myoporaceae) and Pittosporum phylliraeoides var. microcarpa (Pittosporaceae) exhibited antiviral activity against RRV.

In vitro antiviral activity of the anthraquinone chrysophanic acid against poliovirus

Publisher: Elsevier BV

Date: 03-2001

DOI: 10.1016/S0166-3542(01)00125-5

Abstract: Chrysophanic acid (1,8-dihydroxy-3-methylanthraquinone), isolated from the Australian Aboriginal medicinal plant Dianella longifolia, has been found to inhibit the replication of poliovirus types 2 and 3 (Picornaviridae) in vitro. The compound inhibited poliovirus-induced cytopathic effects in BGM (Buffalo green monkey) kidney cells at a 50% effective concentration of 0.21 and 0.02 microgram/ml for poliovirus types 2 and 3, respectively. The compound inhibited an early stage in the viral replication cycle, but did not have an irreversible virucidal effect on poliovirus particles. Chrysophanic acid did not have significant antiviral activity against five other viruses tested: Coxsackievirus types A21 and B4, human rhinovirus type 2 (Picornaviridae), and the enveloped viruses Ross River virus (Togaviridae) and herpes simplex virus type 1 (Herpesviridae). Four structurally-related anthraquinones--rhein, 1,8-dihydroxyanthraquinone, emodin and aloe-emodin were also tested for activity against poliovirus type 3. None of the four compounds was as active as chrysophanic acid against the virus. The results suggested that two hydrophobic positions on the chrysophanic acid molecule (C-6 and the methyl group attached to C-3) were important for the compound's activity against poliovirus.

Erratum to: Spatial analysis of root hemiparasitic shrubs and their hosts: a search for spatial signatures of above- and below-ground interactions

Publisher: Springer Science and Business Media LLC

Date: 02-12-2016

DOI: 10.1007/S11258-016-0684-8

Development and evaluation of a topical anti-inflammatory preparation containing Dodonaea polyandra extract

Publisher: Frontiers Media SA

Date: 24-10-2015

DOI: 10.18433/J38P57

Abstract: Purpose: We have previously reported that the Australian Northern Kaanju (Kuuku I’yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra. Methods: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). Results: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. Conclusions: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Biological activity and LC-MS/MS profiling of extracts from the Australian medicinal plant Acacia ligulata (Fabaceae)

Publisher: Informa UK Limited

Date: 21-04-2017

DOI: 10.1080/14786419.2017.1318383

Abstract: Acacia ligulata A.Cunn. ex Benth. (Fabaceae: Mimosoideae) is a native Australian plant used traditionally by Australian Aboriginal groups. This study was undertaken to investigate the bioactivity of A. ligulata extracts and to evaluate their chemical composition. Potential antibacterial, cytotoxic and enzyme inhibitory effects relevant to traditional medicinal and food uses of the species were examined and LC-MS/MS was performed to investigate the chemical composition. Antibacterial activity was observed for bark and leaf extracts with an MIC for the bark extract of 62.5 μg/mL against Streptococcus pyogenes. Pod extracts showed cytotoxic effects against cancer cells, with the highest activity against melanoma SK-MEL28 cells with IC

Quality and availability of consumer information on heart failure in Australia

Publisher: Springer Science and Business Media LLC

Date: 12-2008

DOI: 10.1186/1472-6963-8-255

Design and synthesis of novel 4-substituted quinazoline-2-carboxamide derivatives targeting AcrB to reverse the bacterial multidrug resistance.

Publisher: Elsevier BV

Date: 12-2020

DOI: 10.1016/J.BIOORG.2020.104394

Evaluation of the anti-inflammatory properties of Dodonaea polyandra, a Kaanju traditional medicine

Publisher: Elsevier BV

Date: 10-2010

DOI: 10.1016/J.JEP.2010.07.012

Abstract: Extracts of the medicinal plant species Dodonaea polyandra were investigated as part of a collegial research partnership between Northern Kaanju traditional owners represented by Chuulangun Aboriginal Corporation (centred on the Wenlock and Pascoe Rivers, Cape York Peninsula, Queensland, Australia) and university-based researchers. D. polyandra, known as "Uncha" in Kaanju language, is used in Northern Kaanju Traditional Medicine for relief from pain associated with toothache and related ailments. The species has a restricted distribution in Cape York Peninsula and there has been no previous Western scientific investigation of its pharmacology or chemistry. The current study investigates the anti-inflammatory effects of several extracts from D. polyandra. Phytochemical screening was conducted using TLC. Anti-inflammatory effects of leaf extracts were determined using an acute mouse ear oedema model induced by croton oil and 12-o-tetradecanoylphorbol-13-acetate (TPA) chemical irritants. Flavonoid and terpenoid secondary compounds were detected in leaf extracts of D. polyandra. Non-polar hexane and methylene chloride/methanol extracts showed potent inhibition of inflammation in TPA-induced mouse ear oedema by 72.12 and 79.81%, respectively, after 24 h at 0.4 mg/ear. In a mouse model of acute inflammation, this study revealed that leaf extracts of D. polyandra possess significant anti-inflammatory potential. These results contribute to a Western scientific understanding of the ethnopharmacological use of the plant in Northern Kaanju Medicine for reducing tooth-related pain.

Serrulatane diterpenoids from the leaves of Eremophila glabra and their potential as antihyperglycemic drug leads

Publisher: Elsevier BV

Date: 04-2022

DOI: 10.1016/J.PHYTOCHEM.2021.113072

Abstract: Eremophila (Scrophulariaceae) is a genus of Australian desert plants, which have been used by Australian Aboriginal people for various medicinal purposes. Crude extracts of the leaf resin of Eremophila glabra (R.Br.) Ostenf. showed α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC

Cinnamaldehyde derivatives act as antimicrobial agents against Acinetobacter baumannii through the inhibition of cell division

Publisher: Frontiers Media SA

Date: 29-08-2022

DOI: 10.3389/FMICB.2022.967949

Abstract: Acinetobacter baumannii is a pathogen with high intrinsic antimicrobial resistance while multidrug resistant (MDR) and extensively drug resistant (XDR) strains of this pathogen are emerging. Treatment options for infections by these strains are very limited, hence new therapies are urgently needed. The bacterial cell ision protein, FtsZ, is a promising drug target for the development of novel antimicrobial agents. We have previously reported limited activity of cinnamaldehyde analogs against Escherichia coli . In this study, we have determined the antimicrobial activity of six cinnamaldehyde analogs for antimicrobial activity against A. baumannii . Microscopic analysis was performed to determine if the compounds inhibit cell ision. The on-target effect of the compounds was assessed by analyzing their effect on polymerization and on the GTPase activity of purified FtsZ from A. baumannii . In silico docking was used to assess the binding of cinnamaldehyde analogs. Finally, in vivo and in vitro safety assays were performed. All six compounds displayed antibacterial activity against the critical priority pathogen A. baumannii , with 4-bromophenyl-substituted 4 displaying the most potent antimicrobial activity (MIC 32 μg/mL). Bioactivity was significantly increased in the presence of an efflux pump inhibitor for A. baumannii ATCC 19606 (up to 32-fold) and significantly, for extensively drug resistant UW 5075 (greater than 4-fold), suggesting that efflux contributes to the intrinsic resistance of A. baumannii against these agents. The compounds inhibited cell ision in A. baumannii as observed by the elongated phenotype and targeted the FtsZ protein as seen from the inhibition of polymerization and GTPase activity. In silico docking predicted that the compounds bind in the interdomain cleft adjacent to the H7 core helix. Di-chlorinated 6 was devoid of hemolytic activity and cytotoxicity against mammalian cells in vitro , as well as adverse activity in a Caenorhabditis elegans nematode model in vivo . Together, these findings present halogenated analogs 4 and 6 as promising candidates for further development as antimicrobial agents aimed at combating A. baumannii . This is also the first report of FtsZ-targeting compounds with activity against an XDR A. baumannii strain.

Navigating through chemical space and evolutionary time across the Australian continent in plant genus Eremophila

Publisher: Cold Spring Harbor Laboratory

Date: 03-11-2020

DOI: 10.1101/2020.11.02.364471

Abstract: Eremophila is the largest genus in the plant tribe Myoporeae (Scrophulariaceae) and exhibits incredible morphological ersity across the Australian continent. The Australian Aboriginal Peoples recognize many Eremophila species as important sources of traditional medicine, the most frequently used plant parts being the leaves. Recent phylogenetic studies have revealed complex evolutionary relationships between Eremophila and related genera in the tribe. Unique and structurally erse metabolites, particularly diterpenoids, are also a feature of plants in this group. To assess the full dimension of the chemical space of the tribe Myoporeae, we investigated the metabolite ersity in a chemo-evolutionary framework applying a combination of molecular phylogenetic and state-of-the-art computational metabolomics tools to build a dataset involving leaf s les from a total of 291 specimens of Eremophila and allied genera. The chemo-evolutionary relationships are expounded into a systematic context by integration of information about leaf morphology (resin and hairiness), environmental factors (pollination and geographical distribution) and medicinal properties (traditional medicinal uses and antibacterial studies) augmenting our understanding of complex interactions in biological systems.

Isolation and structure elucidation of caryophyllane sesquiterpenoids from leaves of Eremophila spathulata

Publisher: Elsevier BV

Date: 02-2022

DOI: 10.1016/J.PHYTOL.2021.12.010

The extent of medication-related hospital admissions in Australia: a review from 1988 to 2021

Publisher: Springer Science and Business Media LLC

Date: 28-01-2022

DOI: 10.1007/S40264-021-01144-1

Catecholic alkaloid sulfonates and aromatic nitro compounds from Portulaca oleracea and screening of their anti-inflammatory and anti-microbial activities.

Publisher: Elsevier BV

Date: 2020

DOI: 10.1016/J.PHYTOCHEM.2020.112587

Antioxidant and Antiglycation Activities of Syzygium paniculatum Gaertn and Inhibition of Digestive Enzymes Relevant to Type 2 Diabetes Mellitus

Publisher: Springer Science and Business Media LLC

Date: 03-10-2020

DOI: 10.1007/S11130-020-00858-4

Serrulatane Diterpenoid from Eremophila neglecta Exhibits Bacterial Biofilm Dispersion and Inhibits Release of Pro-inflammatory Cytokines from Activated Macrophages

Publisher: American Chemical Society (ACS)

Date: 04-12-2015

DOI: 10.1021/ACS.JNATPROD.5B00833

Abstract: The purpose of this study was to assess the biofilm-removing efficacy and inflammatory activity of a serrulatane diterpenoid, 8-hydroxyserrulat-14-en-19-oic acid (1), isolated from the Australian medicinal plant Eremophila neglecta. Biofilm breakup activity of compound 1 on established Staphylococcus epidermidis and Staphylococcus aureus biofilms was compared to the antiseptic chlorhexidine and antibiotic levofloxacin. In a time-course study, 1 was deposited onto polypropylene mesh to mimic a wound dressing and tested for biofilm removal. The ex-vivo cytotoxicity and effect on lipopolysaccharide-induced pro-inflammatory cytokine release were studied in mouse primary bone-marrow-derived macrophage (BMDM) cells. Compound 1 was effective in dispersing 12 h pre-established biofilms with a 7 log10 reduction of viable bacterial cell counts, but was less active against 24 h biofilms (approximately 2 log10 reduction). Compound-loaded mesh showed dosage-dependent biofilm-removing capability. In addition, compound 1 displayed a significant inhibitory effect on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion from BMDM cells, but interleukin-1 beta (IL-1β) secretion was not significant. The compound was not cytotoxic to BMDM cells at concentrations effective in removing biofilm and lowering cytokine release. These findings highlight the potential of this serrulatane diterpenoid to be further developed for applications in wound management.

PTP1B-Inhibiting Branched-Chain Fatty Acid Dimers from Eremophila oppositifolia subsp. angustifolia Identified by High-Resolution PTP1B Inhibition Profiling and HPLC-PDA-HRMS-SPE-NMR Analysis

Publisher: American Chemical Society (ACS)

Date: 07-04-2020

DOI: 10.1021/ACS.JNATPROD.0C00070

VISUALIZATION OF SUB-SURFACE STRUCTURES IN SCAR TISSUE USING OPTICAL COHERENCE TOMOGRAPHY

Publisher: Wiley

Date: 07-2010

DOI: 10.1111/J.1524-475X.2010.00600.X

Serrulatane diterpenoids with unusual side chain modifications from root bark of Eremophila longifolia

Publisher: Elsevier BV

Date: 11-2022

DOI: 10.1016/J.PHYTOCHEM.2022.113408

Abstract: The plant genus Eremophila is endemic to Australia and widespread in arid regions. Root bark extract of Eremophila longifolia (R.Br.) F.Muell. (Scrophulariaceae) was investigated by LC-PDA-HRMS, and dereplication suggested the presence of a series of diterpenoids. Using a combination of preparative- and analytical-scale HPLC separation as well as extensive 1D and 2D NMR analysis, the structures of 12 hitherto unreported serrulatane diterpenoids, eremolongine A-L, were established. These structures included serrulatanes with unusual side chain modifications to form hitherto unseen skeletons with, e.g., cyclopentane, oxepane, and bicyclic hexahydro-1H-cyclopenta[c]furan moieties. Serrulatane diterpenoids in Eremophila have recently been shown to originate from a common biosynthetic precursor with conserved stereochemical configuration, and this was used for tentative assignment of the relative and absolute configuration of the isolated compounds. Triple high-resolution α-glucosidase/α-amylase/PTP1B inhibition profiling demonstrated that several of the eremolongines had weak inhibitory activity towards targets important for management of type 2 diabetes.

Antiproliferative Aporphine Alkaloids from Litsea glutinosa and Ethnopharmacological Relevance to Kuuku I’yu Traditional Medicine

Publisher: CSIRO Publishing

Date: 2015

DOI: 10.1071/CH15456

Abstract: Australian Aboriginal people have a long history of relying on plants for the treatment of various ailments and illnesses. Our ongoing collaborative research project initiated by Chuulangun Aboriginal Corporation (Cape York, Australia) has recently focussed on revealing whether Kuuku I’yu plant medicines possess anticancer-related activities and the chemistry responsible for this. Here, we present results from a study of the plant Litsea glutinosa, used traditionally for the treatment of gastrointestinal disorders. Four known aporphine alkaloids N-methylactinodaphnine (1), boldine (2), N-methyllaurotetanine (3), and isoboldine (4) were isolated by activity-guided fractionation and tested for cytotoxicity against HT29, SKMEL28, and primary human keratinocytes. Compound 1 was the most cytotoxic and this observation may be explained by the presence of a 1,2-methylenedioxy group. In silico docking revealed that a plausible mechanism for the observed cytotoxicity is the stabilization of a topoisomerase II (β) DNA–enzyme complex. The ethnopharmacological relevance of this study is discussed in the context of researching and using traditional knowledge in biomolecular discovery.

Advances in the Use of Anti-inflammatory Agents to Manage Chemotherapy-induced Oral and Gastrointestinal Mucositis

Publisher: Bentham Science Publishers Ltd.

Date: 13-07-2018

DOI: 10.2174/1381612824666180409093918

Abstract: Mucositis is a side effect associated with the use of chemotherapy, and has a significant impact on the quality of life. Mucositis, by definition, refers to the inflammation of the mucosa and occurs throughout the alimentary tract from the mouth to anus. Nuclear Factor kappa B (NFκB) encompasses a family of transcription factors, which upregulate pro-inflammatory cytokines. These are recognized as key targets in developing therapeutic interventions for chemotherapy-induced mucositis, and cyclooxygenase (COX)-2 inhibition may also be beneficial in reducing the severity and duration. This review focuses on the pathobiology of chemotherapy-induced oral and gastrointestinal mucositis and recent research examining the role of agents with anti-inflammatory activity in treatment and prevention of the condition. We consider agents in clinical use as well as some others under current investigation including plant-derived and other natural medicines.

Antimicrobial Action and Reversal of Resistance in MRSA by Difluorobenzamide Derivatives Targeted at FtsZ

Publisher: MDPI AG

Date: 05-12-2020

DOI: 10.3390/ANTIBIOTICS9120873

Abstract: The bacterial cell ision protein, FtsZ, has been identified as a target for antimicrobial development. Derivatives of 3-methoxybenzamide have shown promising activities as FtsZ inhibitors in Gram-positive bacteria. We sought to characterise the activity of five difluorobenzamide derivatives with non-heterocyclic substituents attached through the 3-oxygen. These compounds exhibited antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA), with an isopentyloxy-substituted compound showing modest activity against vancomycin resistant Enterococcus faecium (VRE). The compounds were able to reverse resistance to oxacillin in highly resistant clinical MRSA strains at concentrations far below their MICs. Three of the compounds inhibited an Escherichia coli strain lacking the AcrAB components of a drug efflux pump, which suggests the lack of Gram-negative activity can partly be attributed to efflux. The compounds inhibited cell ision by targeting S. aureus FtsZ, producing a dose-dependent increase in GTPase rate which increased the rate of FtsZ polymerization and stabilized the FtsZ polymers. These compounds did not affect the polymerization of mammalian tubulin and did not display haemolytic activity or cytotoxicity. These derivatives are therefore promising compounds for further development as antimicrobial agents or as resistance breakers to re-sensitive MRSA to beta-lactam antibiotics.

Medication safety in acute care in Australia: where are we now? Part 2: a review of strategies and activities for improving medication safety 2002-2008

Publisher: Springer Science and Business Media LLC

Date: 22-09-2009

DOI: 10.1186/1743-8462-6-24

Self-medication with over-the-counter drugs and complementary medications in South Australia's elderly population

Publisher: Springer Science and Business Media LLC

Date: 11-11-2009

DOI: 10.1186/1472-6882-9-42

Abstract: A number of surveys have examined use of complementary and alternative medicines (CAM) in Australia. However, there are limited Australian data on use of CAM and over-the-counter (OTC) medicines in the elderly population. The main aims of this study were to examine self-medication practices with CAM and OTC medicines among older Australians and variables associated with their use. The Australian Longitudinal Study of Ageing (ALSA) is an ongoing multidisciplinary prospective study of the older population which commenced in 1992 in South Australia. Data collected in 4 waves of ALSA between 1992 and 2004 were used in this study with a baseline s le of 2087 adults aged 65 years and over, living in the community or residential aged care. OTC medicines were classified according to the World Health Organization Anatomical Therapeutic Chemical (ATC) classification. CAM were classified according a modified version of the classification adopted by the Therapeutics Goods Administration (TGA) in Australia. The prevalence of CAM or OTC use ranged from 17.7% in 2000-2001 to 35.5% in 2003-2004. The top classes of CAM and OTC medicines used remained relatively constant over the study period. The most frequent classes of CAM used were vitamins and minerals, herbal medicines and nutritional supplements while the most commonly used OTC were analgesics, laxatives and low dose aspirin. Females and those of younger age were more likely to be CAM users but no variable was associated with OTC use. Participants seemed to self-medicate in accordance with approved indications, suggesting they were informed consumers, actively looking after their own health. However, use of analgesics and aspirin are associated with an increased risk of adverse drug events in the elderly. Future work should examine how self-medication contributes to polypharmacy and increases the risk of adverse drug reactions.

Navigating through chemical space and evolutionary time across the Australian continent in plant genus Eremophila

Publisher: Wiley

Date: 16-09-2021

DOI: 10.1111/TPJ.15448

Abstract: Eremophila is the largest genus in the plant tribe Myoporeae (Scrophulariaceae) and exhibits incredible morphological ersity across the Australian continent. The Australian Aboriginal Peoples recognize many Eremophila species as important sources of traditional medicine, the most frequently used plant parts being the leaves. Recent phylogenetic studies have revealed complex evolutionary relationships between Eremophila and related genera in the tribe. Unique and structurally erse metabolites, particularly diterpenoids, are also a feature of plants in this group. To assess the full dimension of the chemical space of the tribe Myoporeae, we investigated the metabolite ersity in a chemo‐evolutionary framework applying a combination of molecular phylogenetic and state‐of‐the‐art computational metabolomics tools to build a dataset involving leaf s les from a total of 291 specimens of Eremophila and allied genera. The chemo‐evolutionary relationships are expounded into a systematic context by integration of information about leaf morphology (resin and hairiness), environmental factors (pollination and geographical distribution), and medicinal properties (traditional medicinal uses and antibacterial studies), augmenting our understanding of complex interactions in biological systems.

Design and synthesis of benzochromene derivatives as AcrB inhibitors for the reversal of bacterial multidrug resistance

Publisher: Elsevier BV

Date: 03-2023

DOI: 10.1016/J.EJMECH.2023.115148

Polyandric acid A, a clerodane diterpenoid from the australian medicinal plant dodonaea polyandra, attenuates pro-inflammatory cytokine secretion in vitro and in vivo

Publisher: American Chemical Society (ACS)

Date: 08-01-2014

DOI: 10.1021/NP400704B

Abstract: Dodonaea polyandra is a medicinal plant used traditionally by the Kuuku I'yu (Northern Kaanju) indigenous people of Cape York Peninsula, Australia. The most potent of the diterpenoids previously identified from this plant, polyandric acid A (1), has been examined for inhibition of pro-inflammatory cytokine production and other inflammatory mediators using well-established acute and chronic mouse ear edema models and in vitro cellular models. Topical application of 1 significantly inhibited interleukin-1β production in mouse ear tissue in an acute model. In a chronic skin inflammation model, a marked reduction in ear thickness, associated with significant reduction in myeloperoxidase accumulation, was observed. Treatment of primary neonatal human keratinocytes with 1 followed by activation with phorbol ester/ionomycin showed a significant reduction in IL-6 secretion. The present study provides evidence that the anti-inflammatory properties of 1 are due to inhibition of pro-inflammatory cytokines associated with skin inflammation and may be useful in applications for skin inflammatory conditions including psoriasis and dermatitis.

Traditional Australian Aboriginal medicinal plants: An untapped resource for novel therapeutic compounds?

Publisher: Future Science Ltd

Date: 05-2013

DOI: 10.4155/FMC.13.44

Rare, seven-membered cyclic ether labdane diterpenoid from Dodonaea polyandra

Publisher: Elsevier BV

Date: 12-2012

DOI: 10.1016/J.PHYTOCHEM.2012.07.016

Abstract: Previous phytochemical studies on the leaf resin of dioecious plant species Dodonaea polyandra have identified the presence of furanoclerodane diterpenoids. As part of ongoing research on this species the chemical profile of an in idual plant displaying male flowers was investigated. Repeated chromatographic separation of a resinous extract from the leaves of the plant yielded three labdane diterpenoids, 13,17-epoxy-13-methyl-15-oxo-labda-7-ene (1), 17-hydroxy-13-methyl-labda-7,13Z-diene-15-oic acid (2) and 13-methyl-17-oxo-labda-7,13Z-diene-15-oic acid (3) and a fourth known labdane diterpenoid (4) reported as being isolated from a natural source for the first time. Structural elucidation was carried out using conventional 1D and 2D NMR and mass spectrometry together with other complementary techniques (UV and IR). The leaf extract from this in idual of D. polyandra with male flowers present displays a marked difference in the chemical composition of diterpenoids compared to previously studied extracts from the leaves of this species.

The extent of medication errors and adverse drug reactions throughout the patient journey in acute care in Australia

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 09-2016

DOI: 10.1097/XEB.0000000000000075

Quality use of medicines in aged-care facilities in Australia

Publisher: Springer Science and Business Media LLC

Date: 2003

DOI: 10.2165/00002512-200320090-00002

Abstract: Medication-related problems are most commonly reported in elderly patients. It is for this reason that the development of services supporting appropriate medication management in the elderly is paramount particularly for those living in residential care facilities. In 1991, Australia had very limited services supporting the quality use of medicines for residents of aged-care facilities. Over 11 years, from 1991-2002, the range of services has expanded considerably. Federally funded medication review services are now available, with over 80% of residents provided with the service. Medication advisory committees, in accordance with national practice guidelines, have been established in many facilities to address issues concerning medication management. Fifty percent of Australian's pharmacies are registered to provide services, with over 10% of the country's pharmacists accredited to provide the service. National practice guidelines for medication management in aged-care facilities have been incorporated into accreditation standards for aged-care facilities, further integrating activity into the wider health system. The environment was created for these activities through the formation of the Pharmaceutical Health and Rational Use of Medicines (PHARM) Committee, an expert advisory committee, and the Australian Pharmaceutical Advisory Council (APAC), a representative council. Both groups had responsibility for advising the Federal Minister of Health. They both identified medication misadventure in residential aged care as a priority issue and through their recommendations the Government devoted funds to the development of best practice guidelines and research activity. Clinical pharmacy services in nursing-home and hostel settings were found to reduce the use of benzodiazepines, laxatives, NSAIDs and antacids leading to cost savings to the health system. Dose-administration aids were found to reduce error rates during medication administration, and the alteration of medications for administration to residents was found to be common practice and potentially problematic. Research in the Australian setting demonstrating effectiveness, as measured by changes in medication use or health outcomes, as well as actual or potential cost savings has been a critical success factor. In addition, prioritisation by government advisory committees, inquiries and policy documents, have assisted in the development of services from ideas in 1991 to nationally funded realities in 2002.

Flavonoids from the leaves and stems of Dodonaea polyandra: A Northern Kaanju medicinal plant

Publisher: Elsevier BV

Date: 10-2011

DOI: 10.1016/J.PHYTOCHEM.2011.05.006

Abstract: Three prenylated flavonoids 5,7,4'-trihydroxy-3'(3-methylbut-2-enyl)-3-methoxy flavone, 5,7-dihydroxy-3'(3-methylbut-2-enyl)-3,4'-dimethoxy flavone and 5,7,4'-trihydroxy-3',5'(3-methylbuyt-2-enyl)-3-methoxy flavone together with three other known flavonoids were isolated from the medicinal plant Dodonaea polyandra. The plant is used in the traditional medicine system of Northern Kaanju people of Cape York Peninsula, Queensland, Australia. The extracts studied have previously been found to possess anti-inflammatory activity. Successive fractionation of leaf and stem extracts by column and high performance liquid chromatography led to the isolation of these compounds. Their structures were determined using a number of spectroscopic techniques including 1D and 2D NMR and high resolution mass spectroscopy. The structural elucidation is reported herein accompanied by full ¹H and ¹³C NMR spectroscopic data. Spectroscopic data of known compounds was in agreement with that previously reported in literature.

Novel 5-methyl-2-phenylphenanthridium derivatives as FtsZ-targeting antibacterial agents from structural simplification of natural product sanguinarine.

Publisher: Elsevier BV

Date: 06-2018

DOI: 10.1016/J.BMCL.2018.04.015

Abstract: A novel series of 5-methyl-2-phenylphenanthridium derivatives were displayed outstanding activity against a panel of antibiotic-sensitive and -resistant bacteria strains compared with their precursor sanguinarine, ciprofloxacin and oxacillin sodium. Compounds 7 l, 7m and 7n were found to display the most effective activity against five sensitive strains (0.06-2 μg/mL) and three resistant strains (0.25-4 μg/mL). The kinetic profiles indicated that compound 7l possessed the strongest bactericidal effect on S. aureus ATCC25923, with the MBC value of 16 μg/mL. The cell morphology and the FtsZ polymerization assays indicated that these compounds inhibited the bacterial proliferation by interfering the function of bacterial FtsZ. The SARs showed that all the 4-methyl-substituted 5-methyl-2-phenylphenanthridium subseries could be further investigated as the FtsZ-targeting antibacterial agents.

Design, synthesis and biological activity evaluation of novel 2,6-difluorobenzamide derivatives through FtsZ inhibition.

Publisher: Elsevier BV

Date: 02-2017

DOI: 10.1016/J.BMCL.2016.12.081

Abstract: Novel series of 3-substituted 2,6-difluorobenzamide derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their in vitro antibacterial activity against various phenotype of Gram-positive and Gram-negative bacteria, and their cell ision inhibitory activity against three representative strains. As a result, 3-chloroalkoxy derivative 7, 3-bromoalkoxy derivative 12 and 3-alkyloxy derivative 17 were found to exhibit the best antibacterial activity against Bacillus subtilis with MICs of 0.25-1μg/mL, and good activity (MIC<10μg/mL) against both susceptible and resistant Staphylococcus aureus. Additionally, all the three compounds displayed potent cell ision inhibitory activity with MIC values of below 1μg/mL against Bacillus subtilis and Staphylococcus aureus.

Can a digital slide scanner and viewing technique assist the visual scoring for the cytokinesis-block micronucleus cytome assay?

Publisher: Oxford University Press (OUP)

Date: 08-05-2020

DOI: 10.1093/MUTAGE/GEAA013

Abstract: The cytokinesis-block micronucleus cytome (CBMNcyt) assay is a comprehensive method to measure DNA damage, cytostasis and cytotoxicity caused by nutritional, radiation and chemical factors. A slide imaging technique has been identified as a new method to assist with the visual scoring of cells for the CBMNcyt assay. A NanoZoomer S60 Digital Pathology slide scanner was used to view WIL2-NS cells treated with hydrogen peroxide (H2O2) and measure CBMNcyt assay biomarkers using a high-definition desktop computer screen. The H2O2-treated WIL2-NS cells were also scored visually using a standard light microscope, and the two visual scoring methods were compared. Good agreement was found between the scoring methods for all DNA damage indices (micronuclei, nucleoplasmic bridges and nuclear buds) and nuclear ision index with correlation R values ranging from 0.438 to 0.789, P & 0.05. Apoptotic and necrotic cell frequency was lower for the NanoZoomer scoring method, but necrotic frequency correlated well with the direct visual microscope method (R = 0.703, P & 0.0001). Considerable advantages of the NanoZoomer scoring method compared to direct visual microscopy includes reduced scoring time, improved ergonomics and a reduction in scorer fatigue. This study indicates that a digital slide scanning and viewing technique may assist with visual scoring for the CBMNcyt assay and provides similar results to conventional direct visual scoring.

Spatial analysis of root hemiparasitic shrubs and their hosts: a search for spatial signatures of above- and below-ground interactions

Publisher: Springer Science and Business Media LLC

Date: 09-11-2016

DOI: 10.1007/S11258-016-0676-8

Phytochemistry and bioactivity of Acacia sensu stricto (Fabaceae: Mimosoideae)

Publisher: Springer Science and Business Media LLC

Date: 28-06-2019

DOI: 10.1007/S11101-018-9583-Z

Medication safety in acute care in Australia: Where are we now? Part 1: A review of the extent and causes of medication problems 2002-2008

Publisher: Springer Science and Business Media LLC

Date: 11-08-2009

DOI: 10.1186/1743-8462-6-18

Complementary and alternative medicines and dietary interventions in multiple sclerosis: What is being used in South Australia and why?

Publisher: Elsevier BV

Date: 08-2009

DOI: 10.1016/J.CTIM.2009.03.001

Abstract: To investigate the usage patterns of complementary and alternative medicines (CAMs), as well as dietary interventions, by South Australian people with multiple sclerosis (MS). Self-administered postal survey. Questionnaire mailed to recipients of the South Australian (SA) MS Society newsletter (n=1230). Patterns of CAMs use and dietary interventions, reasons for using/not using CAMs in MS, sources of CAMs information and monthly expenditure on CAMs/dietary interventions. A total of 428 surveys were returned (response rate 34.8%) of which 416 met the inclusion criteria for analysis. The majority of SA people with MS who responded reported using CAMs/dietary interventions (64.7%). Respondents with tertiary education and those with mild and moderate disease reported highest CAM use. The most frequently used CAM product categories were vitamins (81.8%), essential fatty acids (80.7%) and minerals (62.5%). Commonly used herbal products included Ginkgo biloba (18.2%) and valerian (16.4%). Popular diets were the low fat (39.8%), low/no sugar (23.8%) and gluten-free (16.4%) diets. The majority of those using CAMs/dietary interventions did so concurrently with conventional treatments (72.1%). Reasons for use included: general health and well-being to alleviate 'general' as well as specific MS symptoms such as muscle weakness, urinary or memory problems and mobility. Conventional health professionals, and friends/family, were the most common sources of information. Monthly expenditure was most commonly AUD$20-49/month. This study reports frequent use of CAM/dietary intervention amongst SA people with MS. The majority of users did so in conjunction with conventional treatments.

Synthesis and antibacterial activity of 5-methylphenanthridium derivatives as FtsZ inhibitors.

Publisher: Elsevier BV

Date: 08-2017

DOI: 10.1016/J.BMCL.2017.06.005

Abstract: 5-Methylphenanthridium derivatives were designed, synthesized and evaluated for their in vitro antibacterial activity and cell ision inhibitory activity against various Gram-positive and -negative bacteria. Among them, compounds 5A2, 5B1, 5B2, 5B3, 5C1 and 5C2 displayed the best on-target antibacterial activity with an MIC value of 4µg/mL against B. subtilis ATCC9372 and S. pyogenes PS, showing over 2-fold better activity than sanguinarine. The SARs showed that the 5-methylphenanthridium derivatives with the alkyl side chains at the 2-postion, especially the straight alkyl side chains exerted better on-target antibacterial activity.

Isolation, structure elucidation and PTP1B inhibitory activity of serrulatane diterpenoids from the roots of Myoporum insulare

Publisher: Elsevier BV

Date: 10-2020

DOI: 10.1016/J.PHYTOL.2020.07.001

Antibacterial Performance of Terpenoids from the Australian Plant Eremophila lucida

Publisher: MDPI AG

Date: 28-09-2021

DOI: 10.3390/ANTIBIOTICS8020063

Abstract: Plants in the Australian genus Eremophila (Scrophulariaceae) have attracted considerable recent attention for their antimicrobial compounds, which possess a wide range of chemical structures. As they are typically associated with the oily-waxy resin layer covering leaves and green branchlets, and Eremophila lucida is prominent among the species containing a pronounced sticky resin layer, this species was considered of interest for assessing its antibacterial constituents. The n-hexane fraction of the crude acetone extract of the leaves exhibited antibacterial activity against Staphylococcus aureus. Isolation led to the known compounds cembratriene, (3Z, 7E, 11Z)-15-hydroxycembra-3,7,11-trien-19-oic acid (1), the sesquiterpenoid, farnesal (2) and the viscidane diterpenoid, 5α-hydroxyviscida-3,14-dien-20-oic acid (3). The purified compounds were tested for antibacterial activity with 2 and 3 showing moderate antibacterial activity against Gram-positive bacteria.

Polypharmacology-Labeled Molecular Networking: An Analytical Technology Workflow for Accelerated Identification of Multiple Bioactive Constituents in Complex Extracts

Publisher: American Chemical Society (ACS)

Date: 20-02-2023

DOI: 10.1021/ACS.ANALCHEM.2C04859

In vitro inhibitory activities of selected Australian medicinal plant extracts against protein glycation, angiotensin converting enzyme (ACE) and digestive enzymes linked to type II diabetes

Publisher: Springer Science and Business Media LLC

Date: 04-11-2016

DOI: 10.1186/S12906-016-1421-5

In vitro metabolism of the anti-inflammatory clerodane diterpenoid polyandric acid A and its hydrolysis product by human liver microsomes and recombinant cytochrome P450 and UDP-glucuronosyltransferase enzymes

Publisher: Informa UK Limited

Date: 14-07-2016

DOI: 10.1080/00498254.2016.1203041

Abstract: 1. The metabolism of the anti-inflammatory diterpenoid polyandric acid A (PAA), a constituent of the Australian Aboriginal medicinal plant Dodonaea polyandra, and its de-esterified alcohol metabolite, hydrolysed polyandric acid A (PAAH) was studied in vitro using human liver microsomes (HLM) and recombinant UDP-glucuronosyltransferase (UGT) and cytochrome P450 (CYP) enzymes. 2. Hydrolysis of PAA to yield PAAH occurred upon incubation with HLM. Further incubations of PAAH with HLM in the presence of UGT and CYP cofactors resulted in significant depletion, with UGT-mediated depletion as the major pathway. 3. Reaction phenotyping utilising selective enzyme inhibitors and recombinant human UGT and CYP enzymes revealed UGT2B7 and UGT1A1, and CYP2C9 and CYP3A4 as the major enzymes involved in the metabolism of PAAH. 4. Analysis of incubations of PAAH with UDP-glucuronic acid-supplemented HLM and recombinant enzymes by UPLC/MS/MS identified three glucuronide metabolites. The metabolites were further characterised by β-glucuronidase and mild alkaline hydrolysis. The acyl glucuronide of PAAH was shown to be the major metabolite. 5. This study demonstrates the in vitro metabolism of PAA and PAAH and represents the first systematic study of the metabolism of an active constituent of an Australian Aboriginal medicinal plant.

Combined Structure- and Ligand-Based Approach for the Identification of Inhibitors of AcrAB-TolC in Escherichia coli

Publisher: American Chemical Society (ACS)

Date: 27-10-2023

DOI: 10.1021/ACSINFECDIS.3C00350

Arid awakening: New opportunities for Australian plant natural product research

Publisher: CSIRO Publishing

Date: 2016

DOI: 10.1071/RJ16004

Abstract: The importance of plants and other natural reserves as sources for biologically important compounds, particularly for application in food and medicine, is undeniable. Herein we provide a historical context of the major scientific research programs conducted in Australia that have been aimed at discovering novel bioactive natural products from terrestrial plants. Generally speaking, the main approaches used to guide the discovery of novel bioactive compounds from natural resources have included random, ethnobotanical and chemotaxonomic strategies. Previous Australian plant natural product research c aigns appear to have lacked the use of a fourth strategy with equally high potential, namely the ecologically guided approach. In addition, many large studies have s led plant material predominantly from tropical regions of Australia, even though arid and semi-arid zones make up 70% of mainland Australia. Therefore, plants growing in arid zone environments, which are exposed to different external stressors (e.g. low rainfall, high ultraviolet exposure) compared with tropical flora, remain an untapped reservoir of potentially novel bioactive compounds. Research of Australian arid zone plants that is ecologically guided creates a new opportunity for the discovery of novel bioactive compounds from plants (and potentially other biota) for application in health care, food and agricultural industries.

Antibacterial constituents of Eremophila alternifolia: An Australian aboriginal traditional medicinal plant

Publisher: Elsevier BV

Date: 04-2016

DOI: 10.1016/J.JEP.2016.02.011

Abstract: For traditional medicinal purposes Aboriginal Australians have utilised numerous plant species, Eremophila alternifolia is among the most prominent. Traditionally, fresh leaves, leaf-infusions and handmade leaf-pastes have been used as both external and internal preparations to provide relief from a variety of conditions. Preparations of the species have been used to treat various infections of skin, eyes and throat including the treatment of septic wounds. These usages suggest that the plant contains antibacterial compounds however, to date they have not been isolated and identified. The present study aimed to identify antibacterial compounds from this important traditionally recorded medicinal species. Bioassay-guided fractionation was used to isolate compounds from the crude leaf-extract. Antibacterial activity of pure compounds was assessed through broth microdilution method by determining both minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). Structure elucidation was performed using spectroscopic techniques such as 1D and 2D nuclear magnetic resonance spectroscopy and high resolution mass spectrometry. Four compounds have been isolated from the leaf-extract they include previously known flavanones [pinobanksin (1), pinobanksin-3-acetate (2) and pinobanksin-3-cinnamate (3)] and a serrulatane diterpene, 8-hydroxyserrulat-14-en-19-oic acid (4). While compound 4 had been found in other Eremophilas, flavanones 2 and 3 are identified for the first time from the genus Eremophila. The flavanone 3 is the most promising antibacterial compound with significant activity (10-20µM) against strains of the Gram-positive bacterium Staphylococcus aureus including methicillin resistant and biofilm forming strains. No activity was observed for any isolated compounds against the Gram-negative bacterium Escherichia coli. The antibacterial activity of the crude extract of E. alternifolia and of the isolated compounds against Gram-positive bacteria provides a Western scientific explanation of the therapeutic modality of this plant species in traditional Aboriginal medicinal practice.

Instability of Antibacterial Serrulatane Compounds from the Australian Plant Species Eremophila duttonii

Publisher: CSIRO Publishing

Date: 2012

DOI: 10.1071/CH11354

Abstract: Hydrophilically substituted diterpenes of the structural class of serrulatanes have attracted attention as novel antibacterial compounds that are effective even against multidrug-resistant Staphylococcus aureus, a key bacterium involved in human infections. The mechanism of action has, however, not been established yet. Available data on structure–activity relationships suggest that the aromatic hydroxy group is essential for activity, and the strongest activity has been found for naphthyl compounds. In this context, it is reported that two highly active serrulatanes isolated from leaf resin of the Australian plant species Eremophila duttonii showed instability upon separation. Acetylation of hydroxy groups generated stable compounds that could be isolated and identified by NMR spectroscopy. The acetylated compounds showed little antibacterial activity, but such activity, as well as oxidative instability, was restored after hydrolysis of the acetate groups. Thus, phenolic hydroxy groups are essential for the mechanism of action of these compounds. The reaction products were not purifiable in sufficient quantities, but indications point to oxidation to quinones. Such oxidation may be a key aspect of the antibacterial activity of this class of compounds.

Bioactivity-guided isolation of compounds from Sophora flavescens with antibacterial activity against Acinetobacter baumannii

Publisher: Informa UK Limited

Date: 10-2021

DOI: 10.1080/14786419.2021.1983570

Abstract: Bioactivity-guided fraction of an extract of

Biodiscoveries within the Australian plant genus Eremophila based on international and interdisciplinary collaboration: results and perspectives on outstanding ethical dilemmas

Publisher: Wiley

Date: 23-07-2022

DOI: 10.1111/TPJ.15866

Abstract: In a cross‐continental research initiative, including researchers working in Australia and Denmark, and based on joint external funding by a 3‐year grant from the Novo Nordisk Foundation, we have used DNA sequencing, extensive chemical profiling and molecular networking analyses across the entire Eremophila genus to provide new knowledge on the presence of natural products and their bioactivities using polypharmocological screens. Sesquiterpenoids, diterpenoids and dimers of branched‐chain fatty acids with previously unknown chemical structures were identified. The collection of plant material from the Eremophila genus was carried out according to a ‘bioprospecting agreement’ with the Government of Western Australia. We recognize that several Eremophila species hold immense cultural significance to Australia's First Peoples. In spite of our best intentions to ensure that new knowledge gained about the genus Eremophila and any potential future benefits are shared in an equitable manner, in accordance with the Nagoya Protocol, we encounter serious dilemmas and potential conflicts in making benefit sharing with Australia's First Peoples a reality.

Identification of new PTP1B-inhibiting decipiene diterpenoid esters from Eremophila clarkei by high-resolution PTP1B inhibition profiling, enzyme kinetics analysis, and molecular docking

Publisher: Elsevier BV

Date: 10-2023

DOI: 10.1016/J.BIOORG.2023.106744

Isolation and Structural Characterization of Echinocystic Acid Triterpenoid Saponins from the Australian Medicinal and Food Plant Acacia ligulata

Publisher: American Chemical Society (ACS)

Date: 04-10-2017

DOI: 10.1021/ACS.JNATPROD.7B00437

Abstract: The Australian plant Acacia ligulata has a number of traditional food and medicinal uses by Australian Aboriginal people, although no bioactive compounds have previously been isolated from this species. Bioassay-guided fractionation of an ethanolic extract of the mature pods of A. ligulata led to the isolation of the two new echinocystic acid triterpenoid saponins, ligulatasides A (1) and B (2), which differ in the fine structure of their glycan substituents. Their structures were elucidated on the basis of 1D and 2D NMR, GC-MS, LC-MS/MS, and saccharide linkage analysis. These are the first isolated compounds from A. ligulata and the first fully elucidated structures of triterpenoid saponins from Acacia sensu stricto having echinocystic acid reported as the aglycone. Compounds 1 and 2 were evaluated for cytotoxic activity against a human melanoma cancer cell line (SK-MEL28) and a diploid fibroblast cell line (HFF), but showed only weak activity.

Antibacterial spectrum and cytotoxic activities of serrulatane compounds from the Australian medicinal plant Eremophila neglecta

Publisher: Oxford University Press (OUP)

Date: 11-2011

DOI: 10.1111/J.1365-2672.2011.05174.X

Abstract: To determine the antibacterial spectrum and cytotoxic activities of serrulatane compounds from the Australian plant Eremophila neglecta. Antimicrobial activities of serrulatane compounds 8,19-dihydroxyserrulat-14-ene (1) and 8-hydroxyserrulat-14-en-19-oic acid (2) were tested against Gram-negative and Gram-positive bacteria including human and veterinary pathogens and some multidrug-resistant isolates. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the compounds were determined by broth microdilution assay. Both compounds exhibited antibacterial activity against all Gram-positive test strains. They showed antimycobacterial activity against isolates of Mycobacterium fortuitum and Mycobacterium chelonae. Of the five Gram-negative bacteria tested, only Moraxella catarrhalis showed susceptibility to the compounds. Cytotoxic activities were tested in the Vero cell line. Compound 1 showed more activity than 2 in both antibacterial and cytotoxicity assays with cytotoxicity at concentrations similar to the MBC. Serrulatane compounds showed significant activity against medically important bacteria, with 1 exhibiting stronger antibacterial activity. However, they also displayed toxicity to mammalian cells. Serrulatanes are of interest as novel antibacterial compounds for use in biomedical applications this study reports data obtained with a range of bacterial strains and mammalian cells, essential for assessing the capabilities and limitations of potential applicability of these compounds.

Substitution of terminal amide with 1H-1,2,3-triazole: Identification of unexpected class of potent antibacterial agents.

Publisher: Elsevier BV

Date: 03-2018

DOI: 10.1016/J.BMCL.2018.02.001

Abstract: 3-Methoxybenzamide (3-MBA) derivatives have been identified as novel class of potent antibacterial agents targeting the bacterial cell ision protein FtsZ. As one of isosteres for the amide group, 1,2,3-triazole can mimic the topological and electronic features of the amide, which has gained increasing attention in drug discovery. Based on these considerations, we prepared a series of 1H-1,2,3-triazole-containing 3-MBA analogues via isosteric replacement of the terminal amide with triazole, which had increased antibacterial activity. This study demonstrated the possibility of developing the 1H-1,2,3-triazole group as a terminal amide-mimetic element which was capable of both keeping and modulating amide-related bioactivity. Surprisingly, a different action mode of these new 1H-1,2,3-triazole-containing analogues was observed, which could open new opportunities for the development of antibacterial agents.

In vivo activity of benzoyl ester clerodane diterpenoid derivatives from dodonaea polyandra

Publisher: American Chemical Society (ACS)

Date: 07-03-2011

DOI: 10.1021/NP100701S

Abstract: Four new benzoyl ester clerodane diterpenoids, 15,16-epoxy-8α-(benzoyloxy)methylcleroda-3,13(16),14-trien-18-oic acid (1), 15,16-epoxy-8α-(benzoyloxy)methyl-2α-hydroxycleroda-3,13(16),14-trien-18-oic acid (2), 15,16-epoxy-8α-(benzoyloxy)methyl-2-oxocleroda-3,13(16),14-trien-18-oic acid (3), and 15,16-epoxy-2α-benzoyloxycleroda-3,13(16),14-trien-18-oic acid (4), have been isolated from the leaves and stems of Dodonaea polyandra. The anti-inflammatory activities of compounds 1, 2, and 4 were evaluated by means of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Compounds 2 and 4 exhibited maximum inhibition of inflammation (70-76%) at doses of 0.22 and 0.9 μmol/ear, respectively. Modest activity (~45% inhibition) was maintained at nanomole/ear doses.

Naturopaths practice behaviour: provision and access to information on complementary and alternative medicines

Publisher: Springer Science and Business Media LLC

Date: 11-07-2005

DOI: 10.1186/1472-6882-5-15

Abstract: The increasing use of complementary and alternative medicines in Australia has generated concern regarding the information on these products available to both healthcare providers and the public. The aim of this study was to examine the practice behaviours of naturopaths in relation to both the provision of and access to information on complementary and alternative medicines (CAM). A representative s le of 300 practicing naturopaths located nationally were sent a comprehensive survey which gathered data on self reported practice behaviour in relation to the provision of information on oral CAM to clients and the information needs of the practitioners themselves A response rate of 35% was achieved. Most practitioners (98%) have a dispensary within their clinic and the majority of practitioners perform the dispensing themselves. Practitioners reported they provided information to clients, usually in the form of verbal information (96%), handwritten notes (83%) and printed information (75%). The majority of practitioners (over 75%) reported always giving information on the full name of the product, reason for prescribing, expected response, possible interactions and contraindications and actions of the product. Information resources most often used by practitioners included professional newsletters, seminars run by manufacturers, patient feedback and personal observation of patients. Most practitioners were positive about the information they could access but felt that more information was required in areas such as adverse reactions and safe use of CAM in children, pregnancy and breastfeeding. Most naturopaths (over 96%) were informed about adverse events through manufacturer or distributor newsletters. The barriers in the provision of information to clients were misleading or incorrect information in the media, time constraints, information overload and complex language used in printed information. The main barrier to the practitioner in information access was seen as the perceived ision between orthodox and complementary medicine practitioners. Our data suggest most naturopaths were concerned about possible interaction between pharmaceuticals and CAM, and explore this area with their patients. There is scope to improve practitioners' access to information of adverse events including an increased awareness of sources of information such as the Australian Therapeutic Goods Administration (TGA) website.

Reversal of ABCG2/BCRP-Mediated Multidrug Resistance by 5,3′,5′-Trihydroxy-3,6,7,4′-Tetramethoxyflavone Isolated from the Australian Desert Plant Eremophila galeata Chinnock

Publisher: MDPI AG

Date: 18-10-2021

DOI: 10.3390/BIOM11101534

Abstract: Multidrug resistance (MDR) is a major challenge in cancer treatment, and the breast cancer resistance protein (BCRP) is an important target in the search for new MDR-reversing drugs. With the aim of discovering new potential BCRP inhibitors, the crude extract of leaves of Eremophila galeata, a plant endemic to Australia, was investigated for inhibitory activity of parental (HT29par) as well as BCRP-overexpressing HT29 colon cancer cells resistant to the chemotherapeutic SN-38 (i.e., HT29SN38 cells). This identified a fraction, eluted with 40% acetonitrile on a solid-phase extraction column, which showed weak growth-inhibitory activity on HT29SN38 cells when administered alone, but exhibited concentration-dependent growth inhibition when administered in combination with SN-38. The major constituent in this fraction was isolated and found to be 5,3′,5′-trihydroxy-3,6,7,4′-tetramethoxyflavone (2), which at a concentration of 25 μg/mL potentiated the growth-inhibitory activity of SN-38 to a degree comparable to that of the known BCRP inhibitor Ko143 at 1 μM. A dye accumulation experiment suggested that 2 inhibits BCRP, and docking studies showed that 2 binds to the same BCRP site as SN-38. These results indicate that 2 acts synergistically with SN-38, with 2 being a BCRP efflux pump inhibitor while SN-38 inhibits topoisomerase-1.

University Of South Australia

Location: Australia

View Organisation

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100139

Start Date: 2021

End Date: 07-2023

Amount: $1,240,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP0667713

Start Date: 04-2006

End Date: 12-2010

Amount: $155,500.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP220200369

Start Date: 07-2023

End Date: 06-2026

Amount: $380,833.00

Funder: Australian Research Council