Anti-Influenza Triterpene Saponins from the Bark of <i>Burkea africana</i>

Mair, Christina E.; Grienke, Ulrike; Wilhelm, Anke; Urban, Ernst; Zehl, Martin; Schmidtke, Michaela; Rollinger, Judith M.

doi:10.1021/acs.jnatprod.7b00774

Cited by 38 publications

(22 citation statements)

References 30 publications

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“…The positive controls LCA (CAS#434-13-9) and CDCA (CAS#474-25-9) were obtained from Sigma Aldrich (Austria). Alphitolic acid (CAS#19533-92-7), was obtained by hydrolysis from a previously isolated saponin (Mair et al, 2018 ). The purity was checked using UPLC-PDA-MS and determined as ≥ 98% for compounds 20 , 21 , 23 , 24 , 28 , 30 - 35 , 37 , 40 , 41 , 44 - 46 , 48 , 49 , and 52 .…”

Section: Methodsmentioning

confidence: 99%

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In Silico Workflow for the Discovery of Natural Products Activating the G Protein-Coupled Bile Acid Receptor 1

et al. 2018

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The G protein-coupled bile acid receptor (GPBAR1) has been recognized as a promising new target for the treatment of diverse diseases, including obesity, type 2 diabetes, fatty liver disease and atherosclerosis. The identification of novel and potent GPBAR1 agonists is highly relevant, as these diseases are on the rise and pharmacological unmet therapeutic needs are pervasive. Therefore, the aim of this study was to develop a proficient workflow for the in silico prediction of GPBAR1 activating compounds, primarily from natural sources. A protocol was set up, starting with a comprehensive collection of structural information of known ligands. This information was used to generate ligand-based pharmacophore models in LigandScout 4.08 Advanced. After theoretical validation, the two most promising models, namely BAMS22 and TTM8, were employed as queries for the virtual screening of natural product and synthetic small molecule databases. Virtual hits were progressed to shape matching experiments and physicochemical clustering. Out of 33 diverse virtual hits subjected to experimental testing using a reporter gene-based assay, two natural products, farnesiferol B (27) and microlobidene (28), were confirmed as GPBAR1 activators reaching more than 50% receptor activation at 20 μM with EC50s of 13.53 μM and 13.88 μM, respectively. This activity is comparable to that of the endogenous ligand lithocholic acid (1). Seven further virtual hits showed activity reaching at least 15% receptor activation either at 5 or 20 μM, including new scaffolds from natural and synthetic origin.

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Section: Methodsmentioning

confidence: 99%

“…For all other compounds it was between 90 and 98%. MS and NMR data of all in house compounds ( 27 , 28 , 52 ) are provided in the literature (Rollinger et al, 2008 ; Mair et al, 2018 ) and the Supplementary Information (Supplementary Figures 4 – 10 ).…”

Section: Methodsmentioning

confidence: 99%

In Silico Workflow for the Discovery of Natural Products Activating the G Protein-Coupled Bile Acid Receptor 1

et al. 2018

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“…69 Two new triterpene saponins (55 and 56) with four undescribed aglycone structures, which were purified from the bark of Burkea Africana, showed significant effects against H3N2 (HK/68) and the 2009 pandemic H1N1 (A/Jena/8178/09) with IC 50 values between 0.05 and 0.27 μM, and CC 50 = 1.5 ± 0.80 μM. 70 Chlorogenin 3-O-β-chacotrioside (60) and chlorogenin 6-α-O-actyl-3-O-β-chacotrioside (61) were discovered as the first novel small molecule inhibitors to effectively block H5N1 viral entry. They exhibited significant inhibitory activity against H5N1 (Goose/Qinghai/59/05 and A/Viet Nam/1203/2004) with IC 50 values between 7.22 and 9.25 μM.…”

Section: F I G U R Ementioning

confidence: 99%

Development of anti‐influenza agents from natural products

Zhang

Morris‐Natschke

Cheng

et al. 2020

Medicinal Research Reviews

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“…FTIR spectra were acquired on a Bruker Tensor 27 spectrometer. 1D and 2D NMR experiments were performed by using a Bruker Avance 500 NMR spectrometer (Ultra-Shield) with a 5-mm switchable probe (TCI Prodigy CryoProbe, 5 mm, triple resonance inverse detection probe head) as described before [26]. The samples (1-2 mg) were measured at 298 K in fully deuterated MeOH referenced to the residual nondeuterated solvent signals.…”

Section: General Experimental Proceduresmentioning

confidence: 99%

Lanostane Triterpenes from Gloeophyllum odoratum and Their Anti-Influenza Effects

et al. 2018

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In an screening for anti-influenza agents from European polypores, the fruit body extract of dose-dependently inhibited the cytopathic effect of the H3N2 influenza virus A/Hong Kong/68 (HK/68) in Madin Darby canine kidney cells with a 50% inhibitory concentration (IC) of 15 µg/mL, a noncytotoxic concentration. After a chromatographic work-up, eight lanostane triterpenes (1: -8: ) were isolated and their structures were elucidated based on high-resolution electrospray ionization mass spectrometry analyses, and one- and two-dimensional nuclear magnetic resonance experiments. Constituents 1: (gloeophyllin K) and 2: (gloeophyllin L) are reported here for the first time, and compounds 5: , 7: , and 8: have not been described for the investigated fungal material so far. The highest activity was determined for trametenolic acid B (3: ) against HK/68 and the 2009 pandemic H1N1 strain A/Jena/8178/09 with IC values of 14 and 11 µM, respectively. In a plaque reduction assay, this compound was able to bind to cell-free viruses and to neutralize their infectivity.

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Anti-Influenza Triterpene Saponins from the Bark of Burkea africana

Cited by 38 publications

References 30 publications

In Silico Workflow for the Discovery of Natural Products Activating the G Protein-Coupled Bile Acid Receptor 1

In Silico Workflow for the Discovery of Natural Products Activating the G Protein-Coupled Bile Acid Receptor 1

Development of anti‐influenza agents from natural products

Lanostane Triterpenes from Gloeophyllum odoratum and Their Anti-Influenza Effects

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