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Publikation

Lam, Y. T. H.; Hoppe, J.; Dang, Q. N.; Porzel, A.; Soboleva, A.; Brandt, W.; Rennert, R.; Hussain, H.; Davari, M. D.; Wessjohann, L.; Arnold, N.; Purpurascenines A–C, azepino-indole alkaloids from Cortinarius purpurascens: Isolation, biosynthesis, and activity studies on the 5-HT2A receptor J. Nat. Prod. 86, 1373-1384, (2023) DOI: 10.1021/acs.jnatprod.2c00716

Three previously undescribed azepino-indole alkaloids, named purpurascenines A−C (1−3), together with the new-to-nature 7-hydroxytryptophan (4) as well as two known compounds, adenosine (5) and riboflavin (6), were isolated from fruiting bodies of Cortinarius purpurascens Fr. (Cortinariaceae). The structures of 1−3 were elucidated based on spectroscopic analyses and ECD calculations. Furthermore, the biosynthesis of purpurascenine A (1) was investigated by in vivo experiments using 13C-labeled sodium pyruvate, alanine, and sodium acetate incubated with fruiting bodies of C. purpurascens. The incorporation of 13C into 1 was analyzed using 1D NMR and HRESIMS methods. With [3-13C]-pyruvate, a dramatic enrichment of 13C was observed, and hence a biosynthetic route via a direct Pictet−Spengler reaction between α-keto acids and 7-hydroxytryptophan (4) is suggested for the biosynthesis of purpurascenines A−C (1−3). Compound 1 exhibits no antiproliferative or cytotoxic effects against human prostate (PC-3), colorectal (HCT-116), and breast (MCF-7) cancer cells. An in silico docking study confirmed the hypothesis that purpurascenine A (1) could bind to the 5-HT2A serotonin receptor’s active site. A new functional 5-HT2A receptor activation assay showed no functional agonistic but some antagonistic effects of 1 against the 5-HT-dependent 5-HT2A activation and likely antagonistic effects on putative constitutive activity of the 5-HT2A receptor.
Publikation

Neubauer, P. R.; Pienkny, S.; Wessjohann, L. A.; Wessjohann, L.; Brandt, W.; Sewald, N.; Predicting the substrate scope of the flavin‐dependent halogenase BrvH ChemBioChem 21, 3282–3288, (2020) DOI: 10.1002/cbic.202000444

The recently described flavin‐dependent halogenase BrvH is able to catalyze both bromination and chlorination of indole, but shows significantly higher bromination activity. BrvH was annotated as a tryptophan halogenase, but does not accept tryptophan as a substrate. Its native substrate remains unknown. A predictive model with the data available for BrvH was analysed. A training set of compounds tested in vitro was docked into the active site of a complete protein model based on the X‐ray structure of BrvH. The atoms not resolved experimentally have been modelled using molecular mechanics force fields to obtain this protein model. Furthermore, docking poses for the substrates and known non‐substrates have been calculated. Parameters like distance, partial charge, and hybridization state have been analysed to derive rules for prediction of activity. With this model for activity of the BrvH, a virtual screening suggested several structures for potential substrates. Some of the thus preselected compounds were tested in vitro and several could be verified as convertible substrates. Based on information on halogenated natural products, a new dataset was created to specifically search for natural products as substrates/products, and virtual screening in this database yielded further hits.
Bücher und Buchkapitel

Francioso, A.; Franke, K.; Villani, C.; Mosca, L.; d’Erme, M.; Frischbutter, S.; Brandt, W.; Sanchez-Lamar, A.; Wessjohann, L.; Insights into the Phytochemistry of the Cuban Endemic Medicinal Plant Phyllanthus orbicularis: Fideloside, a Novel Bioactive 8-C-glycosyl 2,3-Dihydroflavonol (Pinarosa Avato). Molecules 79-92, (2020) ISBN: 978-3-03928-746-8 DOI: 10.3390/books978-3-03928-747-5

Phyllanthus orbicularis (Phyllanthaceae) is an endemic evergreen tropical plant of Cuba that grows in the western part of the island and is used in traditional medicine as an infusion. The aqueous extract of this plant presents a wide range of pharmacological activitiessuch as antimutagenic, antioxidant and antiviral effects. Given the many beneficial effects and the great interest in the development of new pharmacological products from natural sources, the aim of this work was to investigate the phytochemistry of this species and to elucidate the structure of the main bioactive principles. Besides thepresence of several known polyphenols, the major constituent was hitherto not described. The chemical structure of this compound, here named Fideloside, was elucidated by means of HR-ESIMS/MSn, 1D/2D NMR, FT-IR, and ECD as (2R,3R)-(−)-3’,4 ,5,7-tetrahydroxydihydroflavonol-8-C- -D-glucopyranoside. The compound, as well as the plant aqueous preparations, showed promising bioactive properties, i.e., anti-inflammatory capacity in human explanted monocytes, corroborating future pharmacological use for this new natural C-glycosyl flavanonol.
Publikation

Francioso, A.; Franke, K.; Villani, C.; Mosca, L.; d’Erme, M.; Frischbutter, S.; Brandt, W.; Sanchez-Lamar, A.; Wessjohann, L.; Insights into the Phytochemistry of the Cuban Endemic Medicinal Plant Phyllanthus orbicularis: Fideloside, a Novel Bioactive 8-C-glycosyl 2,3-Dihydroflavonol Molecules 24, 2855, (2019) DOI: 10.3390/molecules24152855

Phyllanthus orbicularis (Phyllanthaceae) is an endemic evergreen tropical plant of Cuba that grows in the western part of the island and is used in traditional medicine as an infusion. The aqueous extract of this plant presents a wide range of pharmacological activitiessuch as antimutagenic, antioxidant and antiviral effects. Given the many beneficial effects and the great interest in the development of new pharmacological products from natural sources, the aim of this work was to investigate the phytochemistry of this species and to elucidate the structure of the main bioactive principles. Besides the presence of several known polyphenols, the major constituent was hitherto not described. The chemical structure of this compound, here named Fideloside, was elucidated by means of HR-ESIMS/MSn, 1D/2D NMR, FT-IR, and ECD as (2R,3R)-(−)-3’,4′,5,7-tetrahydroxydihydroflavonol-8-C-β-D-glucopyranoside. The compound, as well as the plant aqueous preparations, showed promising bioactive properties, i.e., anti-inflammatory capacity in human explanted monocytes, corroborating future pharmacological use for this new natural C-glycosyl flavanonol.
Publikation

Otto, A.; Porzel, A.; Westermann, B.; Brandt, W.; Wessjohann, L.; Arnold, N.; Structural and stereochemical elucidation of new hygrophorones from Hygrophorus abieticola (Basidiomycetes) Tetrahedron 73, 1682-1690, (2017) DOI: 10.1016/j.tet.2017.02.013

Four new hygrophorones (1–4) together with the known hygrophorone B12 (5) have been isolated from fruiting bodies of the basidiomycete Hygrophorus abieticola Krieglst. ex Gröger & Bresinsky. Their structures were assigned on the basis of extensive one and two dimensional NMR spectroscopic analyses as well as ESI-HRMS measurements. Among these compounds, two previously undescribed hygrophorone types, named hygrophorone H12 (3) and 2,3-dihydrohygrophorone H12 (4), were identified. The absolute configuration of hygrophorone E12 (2) is suggested based on quantum chemical CD calculations, while a semisynthetic approach in conjunction with computational studies and analysis of NOE interactions allowed the stereochemical assignment of compounds 3 and 4. Additionally, semisynthetic derivatives of hygrophorone B12 (5) were generated by acetylation of the hydroxyl groups. The biological activity of the natural and semisynthetic hygrophorones was evaluated against phytopathogenic organisms, revealing that the α,β-unsaturated carbonyl functionality is likely to be an essential structural feature. Hygrophorone B12 (5) was identified as the most active compound, acting against both ascomycetous fungi and oomycetes.
Publikation

Natalio, F.; Wiese, S.; Brandt, W.; Wessjohann, L.; Reconstitution of Vanadium Haloperoxidase's Catalytic Activity by Boric Acid-Towards a Potential Biocatalytic Role of Boron Chem.-Eur. J. 23, 4973-4980, (2017) DOI: 10.1002/chem.201605230

Boron's unusual properties inspired major advances in chemistry. In nature, the existence and importance of boron has been fairly explored (e.g. bacterial signaling, plant development) but its role as biological catalyst was never reported. Here, we show that boric acid [B(OH)3] can restore chloroperoxidase activity of Curvularia inaequalis recombinant apo‐haloperoxidase's (HPO) in the presence of hydrogen peroxide and chloride ions. Molecular modeling and semi‐empirical PM7 calculations support a thermodynamically highly favored (bio)catalytic mechanism similarly to vanadium haloperoxidases (V‐HPO) in which [B(OH)3] is assumedly located in apo‐HPO's active site and a monoperoxyborate [B(OH)3(OOH)−] intermediate is formed and stabilized by interaction with specific active site amino acids leading ultimately to the formation of HOCl. Thus, B(OH)3−HPO provides the first evidence towards the future exploitation of boron′s role in biological systems.
Publikation

Paudel, G.; Bilova, T.; Schmidt, R.; Greifenhagen, U.; Berger, R.; Tarakhovskaya, E.; Stöckhardt, S.; Balcke, G. U.; Humbeck, K.; Brandt, W.; Sinz, A.; Vogt, T.; Birkemeyer, C.; Wessjohann, L.; Frolov, A.; Osmotic stress is accompanied by protein glycation in Arabidopsis thaliana J. Exp. Bot. 67, 6283-6295, (2016) DOI: 10.1093/jxb/erw395

Among the environmental alterations accompanying oncoming climate changes, drought is the most important factor influencing crop plant productivity. In plants, water deficit ultimately results in the development of oxidative stress and accumulation of osmolytes (e.g. amino acids and carbohydrates) in all tissues. Up-regulation of sugar biosynthesis in parallel to the increasing overproduction of reactive oxygen species (ROS) might enhance protein glycation, i.e. interaction of carbonyl compounds, reducing sugars and α-dicarbonyls with lysyl and arginyl side-chains yielding early (Amadori and Heyns compounds) and advanced glycation end-products (AGEs). Although the constitutive plant protein glycation patterns were characterized recently, the effects of environmental stress on AGE formation are unknown so far. To fill this gap, we present here a comprehensive in-depth study of the changes in Arabidopsis thaliana advanced glycated proteome related to osmotic stress. A 3 d application of osmotic stress revealed 31 stress-specifically and 12 differentially AGE-modified proteins, representing altogether 56 advanced glycation sites. Based on proteomic and metabolomic results, in combination with biochemical, enzymatic and gene expression analysis, we propose monosaccharide autoxidation as the main stress-related glycation mechanism, and glyoxal as the major glycation agent in plants subjected to drought.
Publikation

Otto, A.; Porzel, A.; Schmidt, J.; Brandt, W.; Wessjohann, L.; Arnold, N.; Structure and Absolute Configuration of Pseudohygrophorones A12 and B12, Alkyl Cyclohexenone Derivatives from Hygrophorus abieticola (Basidiomycetes) J. Nat. Prod. 79, 74-80, (2016) DOI: 10.1021/acs.jnatprod.5b00675

Pseudohygrophorones A(12) (1) and B(12) (2), the first naturally occurring alkyl cyclohexenones from a fungal source, and the recently reported hygrophorone B(12) (3) have been isolated from fruiting bodies of the basidiomycete Hygrophorus abieticola Krieglst. ex Gröger & Bresinsky. Their structures were assigned on the basis of extensive one- and two-dimensional NMR spectroscopic analysis as well as ESI-HRMS measurements. The absolute configuration of the three stereogenic centers in the diastereomeric compounds 1 and 2 was established with the aid of (3)JH,H and (4)JH,H coupling constants, NOE interactions, and conformational analysis in conjunction with quantum chemical CD calculations. It was concluded that pseudohygrophorone A(12) (1) is 4S,5S,6S configured, while pseudohygrophorone B(12) (2) was identified as the C-6 epimer of 1, corresponding to the absolute configuration 4S,5S,6R. In addition, the mass spectrometric fragmentation behavior of 1-3 obtained by the higher energy collisional dissociation method allows a clear distinction between the pseudohygrophorones (1 and 2) and hygrophorone B(12) (3). The isolated compounds 1-3 exhibited pronounced activity against phytopathogenic organisms.
Bücher und Buchkapitel

Bojahr, J.; Obst, K.; Brockhoff, A.; Reichelt, K.; Brandt, W.; Pienkny, S.; Ley, J. P.; Wessjohann, L.; Meyerhof, W.; Interaction of novel sweeteners from Mycetia balansae with the human sweet taste receptor (Hofmann, T., et al., eds.). 253-257, (2014)

In times where overweight and diabetes are major health issues, the demand for taste–optimized low-calorie sweeteners and sweetness enhancers is increasing. The consumer’s preference for natural food ingredients has enforced the search for natural sweeteners. A potential source of such a natural non-nutritive sweetener is the Vietnamese plant Mycetia balansae, which is used for sweetening by locals. We have identified the sweet principle of Mycetia balansae using sensory-guided analysis and characterized its action on the human sweet taste receptor with an integrated approach combining homology modelling and cell-based functional receptor expression.
Bücher und Buchkapitel

Backes, M.; Vössing, T.; Aust, S.; Pienkny, S.; Brandt, W.; Wessjohann, L.; Ley, J. P.; Identification of nitrogen-containing flavonoids as a potent bitter masker supported by combined gustophore modeling and docking studies (Hofmann, T., et al., eds.). 29-34, (2014)

Combining (i) a pharmacophore model based on bitter masking actives related to homoeriodictyol and (ii) a homology model of the broadly tuned human bitter receptor hTAS2R10, some new scaffolds for bitter masking compounds based on neoisoflavonoids were deduced. The masking activities of the compounds were predicted via docking of their energy minimized conformers into the putative binding site and subsequent careful analysis of receptor distortion and the number of potential hydrogen bridge bonds. Whereas weak binding candidates showed no masking effect against 500 ppm caffeine, the neoisoflavonoids 3 and 4 and the azaneoisoflavonoids 6 and 7 were able to reduce the bitterness of caffeine by 14 to 34%. Moreover, the new maskers could effectively reduce the bitterness of 100 ppm naringine by about 40-50%.
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