A Grand Challenge. 3. Unbiased Phenotypic Function of Metabolites from Australia Plants and 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 and . The chemical investigations of resulted in the isolation of four new alkaloids, β-lumicolchicosides A-C (-) and γ-lumicolchicoside A (), together with four lumicolchicine derivatives (-) and six colchicine analogues (-) as known structures. The chemical investigations of resulted in the isolation of four new benzoquinolizidine -oxides, tubulosine -oxide (), isotubulosine -oxide (), 9-demethyltubulosine -oxide (), and 9-demethylisotubulosine -oxide (), together with five known benzoquinolizidine alkaloids (-).

Using UHPLC-MS Profiling for the Discovery of New Dihydro-β-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-β-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 .

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.

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.

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

Three new β-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 β-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.

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.

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.

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.

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.

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).

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.

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.

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.

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.