Myrtinols A-F : new anti-inflammatory peltogynoid flavonoid derivatives from the leaves of Australian Indigenous plant Backhousia myrtifolia

Our in-house ethnopharmacological knowledge directed our anti-inflammatory investigation into the leaves of Backhousia mytifolia. Bioassay guided isolation of the Australian indigenous plant Backhousia myrtifolia led to the isolation of six new rare peltogynoid derivatives named myrtinols A–F (1–6) along with three known compounds 4-O-methylcedrusin (7), 7-O-methylcedrusin (8) and 8-demethylsideroxylin (9). The chemical structures of all the compounds were elucidated by detailed spectroscopic data analysis, and absolute configuration was established using X-ray crystallography analysis. All compounds were evaluated for their anti-inflammatory activity by assessing the inhibition of nitric oxide (NO) production and tumor necrosis factor- α (TNF-α) in lipopolysaccharide (LPS) and interferon (IFN)-γ activated RAW 264.7 macrophages. A structure activity relationship was also established between compounds (1–6), noting promising anti-inflammatory potential by compounds 5 and 9 with an IC50 value of 8.51 ± 0.47 and 8.30 ± 0.96 µg/mL for NO inhibition and 17.21 ± 0.22 and 46.79 ± 5.87 µg/mL for TNF-α inhibition, respectively

Tristaenone A : a new anti-inflammatory compound isolated from the Australian Indigenous plant Tristaniopsis laurina

Inspired by ethnopharmacological knowledge, we conducted a bioassay-guided fractionation of the leaves of Tristaniopsis laurina which led to the discovery of a new anti-inflammatory compound, tristaenone A (1). The structure was elucidated by detailed spectroscopic data analysis, and the absolute configuration was established using X-ray crystallography analysis. Tristaenone A (1) suppressed LPS and IFN-γ-induced NO, TNF-α and IL-6 production in RAW 264.7 cells with IC50 values of 37.58 ± 2.45 μM, 80.6 ± 5.82 μM and 125.65 ± 0.34 μM, respectively. It also inhibited NF-κB nuclear translocation by 52.93 ± 14.14% at a concentration of 31.85 μM

From the bush to the brain : preclinical stages of ethnobotanical anti-inflammatory and neuroprotective drug discovery : an Australian example

The Australian rainforest is a rich source of medicinal plants that have evolved in the face of dramatic environmental challenges over a million years due to its prolonged geographical isolation from other continents. The rainforest consists of an inherent richness of plant secondary metabolites that are the most intense in the rainforest. The search for more potent and more bioavailable compounds from other plant sources is ongoing, and our short review will outline the pathways from the discovery of bioactive plants to the structural identification of active compounds, testing for potency, and then neuroprotection in a triculture system, and finally, the validation in an appropriate neuro-inflammatory mouse model, using some examples from our current research. We will focus on neuroinflammation as a potential treatment target for neurodegenerative diseases including multiple sclerosis (MS), Parkinson’s (PD), and Alzheimer’s disease (AD) for these plant-derived, anti-inflammatory molecules and highlight cytokine suppressive anti-inflammatory drugs (CSAIDs) as a better alternative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) to treat neuroinflammatory disorders

Angiolactone, a new Butyrolactone isolated from the terrestrial myxobacterium, Angiococcus sp.

Myxobacteria are recognized as one of the outstanding prokaryotic sources of bioactive compounds in nature. More than 100 core structures with diverse biological activities had been elucidated, most of which were novel. In the continuous screening program for anti-infectives focusing on novel, rare, and unexplored myxobacterial taxa, great potential was discovered in Angiococcus disciformis SBAn001. The strain was routinely cultivated in TS-6 medium (Tryptone (Difco) 0.6%, MgSO4 - 7H2O 0.2%, soluble starch (Roth) 0.4%, HEPES 1.19%, pH adjusted to 7.2 with KOH before autoclaving)

Potential anti-neuroinflammatory compounds from Australian plants : a review

Neuroinflammation is a complex response to brain injury involving the activation of glia, release of inflammatory mediators, such as cytokines and chemokines, and generation of reactive oxygen and nitrogen species. Even though it is considered an event secondary to neuronal death or dysfunction, neuro-inflammation comprises a majority of the non-neuronal contributors to the cause and progression of neurodegenerative diseases like Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), Chronic Traumatic Encephalopathy (CTE) and others. As a result of the lack of effectiveness of current treatments for neurodegenerative diseases, neuroinflammation has become a legitimate therapeutic target for drug discovery, leading to the study of various in vivo and in vitro models of neuroinflammation. Several molecules sourced from plants have displayed anti-inflammatory properties in the study of neurodegenerative diseases. A group of these anti-inflammatory compounds has been classified as cytokine-suppressive anti-inflammatory drugs (CSAIDs), which target the pro-inflammatory AP1 and nuclear factor-κB signaling pathways and inhibit the expression of many pro-inflammatory cytokines, such as interleukin IL-1, IL-6, TNF-α, or nitric oxide. Australian plants, thriving amid the driest inhabited continent of the world, are an untapped source of chemical diversity in the form of secondary metabolites. These compounds are produced in response to biotic and abiotic stresses that the plants are exposed to in the highly biodiverse environment. This review is an attempt to highlight anti-inflammatory compounds isolated from Australian plants

Lorneic acids C and D, new trialkyl-substituted aromatic acids isolated from a terrestrial Streptomyces sp.

Our ongoing research into the chemical diversity of terrestrial actinomycetes associated with the plant rhizosphere has led to the discovery of rare metabolites, such as leopolic acid A1 and juniperolide A,2 which were isolated from Streptomyces sp. cultured from the rhizosphere of the plant Juniperus excelsa

Pimprinols A-C, from the terrestrial actinomycete, Streptomyces sp.

A Streptomyces sp. Lv3-13, isolated from the rhizosphere soil of the plant Mespilus germanica, has yielded three new pimprinine derivatives, named pimprinols A-C (1-3) and the unknown (2-aminophenyl)(2-ethyloxazol-5-yl) methanone (4) along with the known compounds 2-ethyl oxazole pimprinine and 2-propyl oxazole pimprinine. The structures of the compounds were elucidated based on spectroscopic methods including UV, HR-ESIMS and 1D, 2D NMR data. Compounds 1-4 were screened for antimicrobial and cytotoxic activities

Cryptocaryoic acids A - C : new phenyl alkyl acids isolated from the leaves of Australian rainforest plant Cryptocarya mackinnoniana

Phytochemical investigation of the leaves of the Australian rainforest tree Cryptocarya mackinnoniana led to the discovery of three new oxygenated phenyl alkyl acids, cryptocaryoic acids A – C and two known compounds, cryptocaryone and 2′ ,6′ -dihydroxy-4′ -methoxychalcone. The structures of all the compounds were determined by detailed spectroscopic analysis. Mosher’s analysis was used for absolute stereochemistry determination at C-11, while the remaining stereochemistry determination of the one remaining stereocenter C-13 was based on NOESY correlations. All compounds isolated were also evaluated for their anti-inflammatory properties by assessing their inhibitory effects on LPS and interferon-γ induced nitric oxide (NO) production and TNF- α release in RAW 264.7 macrophages. The new cryptocaryoic acids exhibited weak to moderate anti-inflammatory activity (NO inhibition) ranging from (18.4–56 μM)

Leopolic acid A, isolated from a terrestrial actinomycete, Streptomyces sp.

Chemical analysis of a terrestrial-derived Streptomyces sp. isolated from the rhizosphere of the plant Juniperus excels collected from the Crimean Mountains (Ukraine) yielded a new acid, leopolic acid A (1). Leopolic acid A (1) was identified to possess a rare ureido dipeptide, Phe-CO-Val, attached to a 5-dihydro-3-hydroxy-pyrrole-2-one ring. A detailed spectroscopic and Marfey’s analysis led to the structure elucidation of leopolic acid A (1)

Cystodienoic acid : a new diterpene isolated from the myxobacterium Cystobacter sp.

Myxobacteria are Gram-negative bacteria that are sources of a large number of compounds with unique structures that possess varying biological activities. They are known to produce secondary metabolites that have more novel structures with those produced by other microbes such as, actinomycetes and fungi. In our search for novel secondary metabolites, Cystobacter ferrugineus strain Cbfe23, which was isolated from a soil sample in China, garnered our attention based on our in-house LC–MS analysis. Specifically, a peak identified with an m/z of 352 did not produce any hits in our mass spectral library of compounds, prompting us to further investigate the strain in detail in order to determine the structural profile of the unknown metabolite