Antimicrobial Benzyltetrahydroisoquinoline-Derived Alkaloids from the Leaves of Doryphora aromatica.

Four new alkaloids, (R)-nomimantharine trifluoroacetate (2), 12-demethylphaeantharine trifluoroacetate (3), nominanthranal trifluoroacetate (4), and the enolic form of 1-hydroxy-6,7-dimethoxy-2-methylisoquinoline trifluoroacetate (5), together with the known dimeric alkaloid phaeantharine trifluoroacetate (1), have been isolated from the extract of the leaves of the rainforest tree Doryphora aromatica (Monimiaceae). The structures of these compounds were elucidated by HRMS and 1D and 2D NMR data. (R)-Nomimantharine trifluoroacetate (2) contains an ether linkage connecting a benzylisoquinoline unit with a tetrahydroisoquinoline, a novel class of dimeric alkaloid. The absolute configuration of (R)-nomimantharine trifluoroacetate (2) was established via electronic circular dichroism data. The compounds isolated were subjected to in vitro antimicrobial assays against a panel of pathogenic microorganisms, including Mycobacterium smegmatis, M. tuberculosis, Escherichia coli, Staphylococcus aureus (SA), and five clinical isolates of oxacillin/methicillin-resistant S. aureus (MRSA). Phaeantharine trifluoroacetate (1) and (R)-nomimantharine trifluoroacetate (2) showed moderate inhibitory activities against Mycobacteria and MRSA strains.

A Grand Challenge. 3. Unbiased Phenotypic Function of Metabolites from Australia Plants Gloriosa superba and Alangium villosum against Parkinson's Disease.

As part of a continuing research program aiming to identify chemical probes to interrogate Parkinson's disease (PD), we have investigated the Australian plants Gloriosa superba and Alangium villosum. The chemical investigations of G. superba resulted in the isolation of four new alkaloids, ß-lumicolchicosides A-C (1-3) and γ-lumicolchicoside A (4), together with four lumicolchicine derivatives (5-8) and six colchicine analogues (9-14) as known structures. The chemical investigations of A. villosum resulted in the isolation of four new benzoquinolizidine N-oxides, tubulosine Nß5-oxide (15), isotubulosine Nα5-oxide (16), 9-demethyltubulosine Nß5-oxide (17), and 9-demethylisotubulosine Nα5-oxide (18), together with five known benzoquinolizidine alkaloids (19-23). The chemical structures of the new compounds (1-4 and 15-18) were characterized unambiguously by extensive analysis of their NMR and MS data. Unbiased multidimensional profiling was used to investigate the phenotypic profiles of all of the metabolites. The results show that the lead probes have different effects on cellular organelles that are implicated in PD in patient-derived cells.

Using UHPLC-MS Profiling for the Discovery of New Dihydro-ß-Agarofurans from Australian Celastraceae Plant Extracts.

An analytical method using UHPLC-MS was developed and applied to 16 crude CH2Cl2 extracts from Australian Celastraceae plants; the endemic plant materials were accessed from Griffith University's NatureBank resource and included bark, fruit, leaf, root, twig and mixed samples, all of which were collected from Queensland, Australia. The generated UHPLC-MS data were analysed and dereplicated using the scientific databases Dictionary of Natural Products and SciFinder Scholar in order to potentially identify new dihydro-ß-agarofurans from local Celastraceae plants. These investigations led to the large-scale extraction and isolation work on a prioritised fruit sample that belonged to the rainforest plant Denhamia celastroides. Chemical investigations resulted in the purification of four new natural products, denhaminols O⁻R (1⁻4), along with the related and known compound, denhaminol G (5). The structures of all the new compounds were determined via detailed analysis of NMR and MS data.

LAT Transport Inhibitors from Pittosporum venulosum Identified by NMR Fingerprint Analysis.

(1)H NMR fingerprints were used as the guiding principle for the isolation of minor compounds related to the l-type amino acid transporter inhibitors venulosides A (1) and B (2). Two new monoterpene glycosides, namely, venulosides C (3) and D (4), were isolated from a Queensland collection of the plant Pittosporum venulosum. Compounds 3 and 4 were found to inhibit l-leucine transport in LNCaP cells with IC50 values of 11.47 and 39.73 µM, respectively. The venulosides are the first reported natural product inhibitors of leucine transport in prostate cancer cells, and the isolation of the minor compounds provides some early SAR information.

Watsonianone A-C, anti-plasmodial ß-triketones from the Australian tree, Corymbia watsoniana.

Three new ß-triketones, watsonianones A-C, and the known compound corymbone B were isolated from the flowers of the Australian eucalypt Corymbia watsoniana. Watsonianone A is the first naturally occurring methylene bridged bis-tetramethylcyclohexatrione, watsonianone B is only the fourth fused bisfurano ß-triketone and watsonianone C is the first 4,4a,9,9a-tetrahydro-2H-xanthene-1,3,5,7(6H,8H)-tetraone to be reported in the literature. MS and NMR analysis established the structures of the new compounds. All three new compounds showed anti-plasmodial activity against chloroquine resistant (Dd2) and sensitive strains (3D7) of the parasite, Plasmodium falciparum, responsible for malarial infections. Watsonianone B was the most potent inhibitor (IC(50) 0.289 µM vs. Pf 3D7) demonstrating significant selectivity against the human cell line, HEK 293 (>400 ×). Stage specificity studies indicate that watsonianone B is predominantly active against young ring stages of P. falciparum.

The Herbarium 2021 Half-Earth Challenge Dataset and Machine Learning Competition.

Herbarium sheets present a unique view of the world's botanical history, evolution, and biodiversity. This makes them an all-important data source for botanical research. With the increased digitization of herbaria worldwide and advances in the domain of fine-grained visual classification which can facilitate automatic identification of herbarium specimen images, there are many opportunities for supporting and expanding research in this field. However, existing datasets are either too small, or not diverse enough, in terms of represented taxa, geographic distribution, and imaging protocols. Furthermore, aggregating datasets is difficult as taxa are recognized under a multitude of names and must be aligned to a common reference. We introduce the Herbarium 2021 Half-Earth dataset: the largest and most diverse dataset of herbarium specimen images, to date, for automatic taxon recognition. We also present the results of the Herbarium 2021 Half-Earth challenge, a competition that was part of the Eighth Workshop on Fine-Grained Visual Categorization (FGVC8) and hosted by Kaggle to encourage the development of models to automatically identify taxa from herbarium sheet images.

Hasubanan alkaloids with delta-opioid binding affinity from the aerial parts of Stephania japonica.

Two new (1 and 2) and six known hasubanan alkaloids (3-8) and one morphinane alkaloid (9) were isolated from the leaves of the North Queensland rainforest vine Stephania japonica. The structures of 1 and 2 were determined by interpretation of their 1D and 2D NMR spectra. The hasubanan alkaloids showed affinity for the human delta-opioid receptor with IC(50) values ranging from 0.7 to 46 microM. The compounds were also tested for their affinity to micro- and kappa-opioid receptors and shown to be inactive against kappa-opioid receptors, but were of similar potency against the micro-opioid receptor.

Foliar Mn accumulation in eastern Australian herbarium specimens: prospecting for 'new' Mn hyperaccumulators and potential applications in taxonomy.

BACKGROUND AND AIMS: The analysis of herbarium specimens has previously been used to prospect for 'new' hyperaccumulators, while the use of foliar manganese (Mn) concentrations as a taxonomic tool has been suggested. On the basis of their geographic and taxonomic affiliations to known Mn hyperaccumulators, six eastern Australian genera from the Queensland Herbarium collection were sampled for leaf tissue analyses. METHODS: ICP-OES was used to measure Mn and other elemental concentrations in 47 species within the genera Austromyrtus, Lenwebbia, Gossia (Myrtaceae), Macadamia (Proteaceae), Maytenus and Denhamia (Celastraceae). KEY RESULTS: The resulting data demonstrated (a) up to seven 'new' Mn hyperaccumulators, mostly tropical rainforest species; (b) that one of these 'new' Mn hyperaccumulators also had notably elevated foliar Ni concentrations; (c) evidence of an interrelationship between foliar Mn and Al uptake among the Macadamias; (d) considerable variability of Mn hyperaccumulation within Gossia; and (e) the possibility that Maytenus cunninghamii may include subspecies. CONCLUSIONS: Gossia bamagensis, G. fragrantissima, G. sankowsiorum, G. gonoclada and Maytenus cunninghamii were identified as 'new' Mn hyperaccumulators, while Gossia lucida and G. shepherdii are possible 'new' Mn hyperaccumulators. Of the three Myrtaceae genera examined, Mn hyperaccumulation appears restricted to Gossia, supporting its recent taxonomic revision. In the context of this present investigation and existing information, a reassesment of the general definition of Mn hyperaccumulation may be warranted. Morphological variation of Maytenus cunninghamii at two extremities was consistent with variation in Mn accumulation, indicating two possible 'new' subspecies. Although caution should be exercised in interpreting the data, surveying herbarium specimens by chemical analysis has provided an effective means of assessing foliar Mn accumulation. These findings should be followed up by field studies.

Small-molecule inhibitors of the cancer target, isoprenylcysteine carboxyl methyltransferase, from Hovea parvicalyx.

Isoprenylcysteine carboxyl methyltransferase (Icmt) is enzyme target in anticancer drug discovery. An Icmt natural product high-throughput screening campaign was conducted and a hit extract from the roots of Hovea parvicalyx was identified. 2'-Methoxy-3'-prenyl-licodione and 2'-methoxy-3',3''-diprenyl-licodione, two prenylated beta-hydroxychalcone compounds, together with the known flavanone (S)-glabrol, were isolated and identified as bioactive constituents. Their structures were determined largely by 1D and 2D NMR spectroscopy.

Lysianadioic acid, a carboxypeptidase B inhibitor from Lysiana subfalcata.

A new natural product, lysianadioic acid, was isolated from the plant Lysiana subfalcata as a carboxypeptidase B (CPB) inhibitor. It is a potent inhibitor of CPB with an IC(50) of 0.36 microM. This is the first known example of a small molecule CPB inhibitor isolated from plant origin. Its structure was determined by NMR spectroscopy.

Prenylated dihydrochalcones from Boronia bipinnata that inhibit the malarial parasite enzyme target hemoglobinase II.

High-throughput screening of a plant and marine invertebrate extract library to find natural products that inhibit the malarial parasite enzyme target hemoglobinase II led to the isolation of two new active prenylated chalcones, bipinnatones A (1) and B (2), from aerial parts of the Queensland shrub Boronia bipinnata. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Compounds 1 and 2 inhibited hemoglobinase II with IC 50 values of 64 and 52 microM, respectively.

Myrtucommulones F-I, phloroglucinols with thyrotropin-releasing hormone receptor-2 binding affinity from the seeds of Corymbia scabrida.

High-throughput screening of a plant and marine invertebrate extract library to find natural products with rat thyrotropin-releasing hormone (TRH) receptor-2 binding affinity led to the isolation of four new, myrtucommulones F-I (3-6), and two known, myrtucommulones A (1) and D (2), active acylphloroglucinols from the seeds of the Queensland tree Corymbia scabrida. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. The relative configuration of the stereogenic centers for all six compounds was deduced from ROESY correlations. This is the first time that myrtucommulone A (1) has been isolated as a single pure compound. The structure of myrtucommulone D (2) has been revised. Myrtucommulones A, D, and F-I showed rat TRH receptor-2 binding affinity with IC50 values of 39, 11, 16, 24, 31, and 16 microM, respectively.

Alkaloids from the Australian rainforest tree Ochrosia moorei.

High-throughput screening of a plant and marine invertebrate extract library to find natural products that down-regulate expression of pro-inflammatory genes associated with the glucocorticoid receptor ligand complex led to the identification of bioactive CH2Cl 2 extracts from stems and leaves of the Queensland tree Ochrosia moorei. Bioassay-guided purification of the stem extract enabled the isolation of four alkaloids including two new compounds, ochrosamines A (1) and B (2), and the known compounds ellipticine (3) and 9-methoxyellipticine (4). The leaf extract also afforded 3 and 4 as well as apparicine (5) and desoxycordifoline (6). The structures of the two new compounds were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Ellipticine and 9-methoxyellipticine were the most active components, and both displayed IC 50 values of 90 microM. Apparicine and desoxycordifoline were only very weakly active, and ochrosamines A and B were inactive.

5,6,7,3',4',5'-Hexamethoxyflavone from the Australian plant Eremophila debilis (Myoporaceae).

The aerial parts of the endemic Australian plant Eremophila debilis (Myoporaceae) contain 3% dry weight of the biologically active 5,6,7,3',4',5'-hexamethoxyflavone, which had its structured confirmed using X-ray crystal crystallography. The presence of significant levels of the polypharmacologically active 5,6,7,3',4',5'-hexamethoxyflavone in the edible parts of the plant has potential implications for its use as a food and bush medicine.

Impact of Austropuccinia psidii (myrtle rust) on Myrtaceae-rich wet sclerophyll forests in south east Queensland.

In April 2010, Austropuccinia psidii (formerly Puccinia psidii) was detected for the first time in Australia on the central coast of New South Wales. The fungus spread rapidly along the east coast and can now be found infecting vegetation in a range of native forest ecosystems with disease impacts ranging from minor leaf spots to severe shoot and stem blight and tree dieback. Localised extinction of some plant species has been recorded. In 2014, the impact of A. psidii was observed for the first time in a wet sclerophyll site with a rainforest understory, dominated by species of Myrtaceae, in Tallebudgera Valley, south east Queensland, Australia. This study aimed to determine the impact of A. psidii on individual species and species composition. Here we provide quantitative and qualitative evidence on the significant impact A. psidii has in native ecosystems, on a broader range of species than previously reported. Archirhodomyrtus beckleri, Decaspermum humile, Gossia hillii and Rhodamnia maideniana are in serious decline, with significant increases in tree mortality over the period of our study. This research further highlights the potential of this invasive pathogen to negatively impact native ecosystems and biodiversity.

Mapping biodiversity and setting conservation priorities for SE Queensland's rainforests using DNA barcoding.

Australian rainforests have been fragmented due to past climatic changes and more recently landscape change as a result of clearing for agriculture and urban spread. The subtropical rainforests of South Eastern Queensland are significantly more fragmented than the tropical World Heritage listed northern rainforests and are subject to much greater human population pressures. The Australian rainforest flora is relatively taxonomically rich at the family level, but less so at the species level. Current methods to assess biodiversity based on species numbers fail to adequately capture this richness at higher taxonomic levels. We developed a DNA barcode library for the SE Queensland rainforest flora to support a methodology for biodiversity assessment that incorporates both taxonomic diversity and phylogenetic relationships. We placed our SE Queensland phylogeny based on a three marker DNA barcode within a larger international rainforest barcode library and used this to calculate phylogenetic diversity (PD). We compared phylo- diversity measures, species composition and richness and ecosystem diversity of the SE Queensland rainforest estate to identify which bio subregions contain the greatest rainforest biodiversity, subregion relationships and their level of protection. We identified areas of highest conservation priority. Diversity was not correlated with rainforest area in SE Queensland subregions but PD was correlated with both the percent of the subregion occupied by rainforest and the diversity of regional ecosystems (RE) present. The patterns of species diversity and phylogenetic diversity suggest a strong influence of historical biogeography. Some subregions contain significantly more PD than expected by chance, consistent with the concept of refugia, while others were significantly phylogenetically clustered, consistent with recent range expansions.

Cardenolide glycosides from Elaeodendron australe var. integrifolium.

Extracts from dried leaf and stems of Elaeodendron australe var. integrifolium (Celastraceae) collected in South East Queensland, Australia, were active in an assay that measured Ca(2+) driven expression of IL-2/luciferase designed to identify inhibitors of the ICRAC channel. Bioassay-guided isolation using C18 and polyamide column chromatography, HPLC (Phenyl and C18) and centrifugal partition chromatography (CPC) led to the isolation of digitoxigenin (1) and three cardenolide glycosides, glucoside 2, quinovoside 3 and the new natural product xyloside 4, as the active components with low nM activity in the reporter assay.

Corymbones A and B, phloroglucinols with thyrotropin releasing hormone receptor 2 binding affinity from the flowers of Corymbia peltata.

High-throughput screeing of a plant and marine invertebrate extract library to find natural products with rat thytotropin releasing hormone receptor 2 binding affinity led to the isolation of two new active acylphloroglucinols, corymbones A and B (1 and 2) from flowers of the Queensland tree Corymbia peltata. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Compounds 1 and 2 showed rat TRH receptor 2 binding affinity with IC 50 values of 23 and 19 microM, respectively.

Alkaloids with human delta-opioid receptor binding affinity from the Australian rainforest tree Peripentadenia mearsii.

Three new pyrrolidine alkaloids, peripentonine A-C ( 2- 4), one known pyrrolidine alkaloid, peripentadenine ( 1), and one novel indolizidine alkaloid, mearsamine ( 5), were isolated from the leaves of Peripentadenia mearsii and their structures determined by 1D and 2D NMR spectroscopy. Peripentonines A ( 2) and B ( 3) were isolated as a 1:1 mixture of inseparable diastereomers. Mearsamine ( 5) contains a novel tricyclic ring system. Peripentadenine and peripentonines A/B and C showed receptor binding affinity for the human delta-opioid receptor with IC 50 values of 11.4, 69.2, and 30.9 microM, respectively. Mearsamine did not bind to the delta-opioid receptor.

Endiandrin A, a potent glucocorticoid receptor binder isolated from the Australian plant Endiandra anthropophagorum.

Bioassay-guided fractionation of the DCM extract from the roots of Endiandra anthropophagorum resulted in the isolation of a new cyclobutane lignan, endiandrin A (1), together with the known natural products nectandrin B (2) and (-)-dihydroguaiaretic acid (3). The structure of 1 was determined by extensive 1D and 2D NMR and MS data analyses. Acetylation and methylation of 1 yielded di-O-acetylendiandrin A (4) and di-O-methylendiandrin A (5), respectively. All compounds were tested in a glucocorticoid receptor binding assay and displayed IC50 values ranging from 0.9 to 35 microM.