Biologically Active Secondary Metabolites from Fungi. Part. 21. X-Ray Structure Determination, Absolute Configuration and Biological Activity of Phomoxanthone A.

AbstractIsoselenocyanates (ISCs) are a class of organoselenium compounds that have been recognized as potential chemotherapeutic and chemopreventative agents against cancer(s) and infectious diseases. ISC compounds are chemically analogous to their isosteric relatives, isothiocyanates (ITCs); however, they possess increased biological activity, such as enhanced cytotoxicity against cancer cells. ISCs not only serve as significant products, but also as precursors and essential intermediates for a variety of organoselenium compounds, such as selenium-containing heterocycles, which are biologically active. While syntheses of ISCs have become less difficult to accomplish, the syntheses of selenium-containing heterocycles are often difficult due to the use of highly toxic selenium reagents. Because of this, ISCs can serve as versatile reagents for the preparation of these heterocycles. In this review, the classical and recent syntheses of ISCs will be discussed, along with notable and recent synthetic work employing ISCs to access novel selenium-containing heterocycles.1 Introduction1.1 Selenium and Health2 Isoselenocyanates2.1 Preparation of Isoselenocyanates3 Selenium-Containing Heterocycles3.1 Notable Synthetic Work3.2 Recent Synthetic Work3.2.1 Synthesis of N-(3-Methyl-4-phenyl-3H-selenazol-2-ylidene)benzamide Derivatives3.2.2 Synthesis and X-ray Studies of Diverse Selenourea Derivatives3.2.3 Synthesis of Heteroarene-Fused [1,2,4]Thiadiazoles/Selenadiazoles via Iodine-Promoted [3+2] Oxidative Cyclization3.2.4 2-Amino-1,3-selenazole Derivatives via Base-Promoted Multicomponent Reactions4 Conclusion

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Étude conformationnelle de cétopipérazines: (I) 3R-méthyl-6-carbéthoxy-2 oxopipérazine, (II) 3R-[p-hydroxybenzyl]-6-carbéthoxy-2 oxopipérazine: I, II en solution et structure cristalline de II

Canadian Journal of Chemistry ◽

10.1139/v87-218 ◽

1987 ◽

Vol 65 (6) ◽

pp. 1308-1312 ◽

Cited By ~ 3

Author(s):

André Michel ◽

Guy Evrard ◽

B. Norberg

Keyword(s):

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Absolute Configuration ◽

Structure Determination ◽

Opiate Receptor ◽

Receptor Level ◽

X Ray ◽

Diastereomeric Mixture ◽

The Absolute

The synthesis of the title compounds has been described recently. It was anticipated that the product would be a diastereomeric mixture. Surprisingly, only one isomer was obtained. The present work is an attempt to find the conformationnal properties accounting for those observations. X-ray structure determination of 3R-[p-hydroxybenzyl]-6-carbethoxy-2-oxopiperazine shows that the molecule adopts a folded conformation and that the absolute configuration at C6 is [R]. Investigation in solution using 1H nuclear magnetic resonance shows the existence of three conformers and discusses the relative populations. Those findings are also relevant in terms of the activity of such compounds at the opiate receptor level.

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Monoterpenes as a renewable source of biologically active compounds

Pure and Applied Chemistry ◽

10.1515/pac-2017-0109 ◽

2017 ◽

Vol 89 (8) ◽

pp. 1105-1117 ◽

Cited By ~ 33

Author(s):

Nariman F. Salakhutdinov ◽

Konstantin P. Volcho ◽

Olga I. Yarovaya

Keyword(s):

Biological Activity ◽

Absolute Configuration ◽

Biologically Active Compounds ◽

Biologically Active ◽

Great Promise ◽

Active Compounds ◽

Renewable Source ◽

The Creation ◽

Anti Inflammatory

AbstractMonoterpenes and their derivatives play an important role in the creation of new biologically active compounds including drugs. The review focuses on the data on various types of biological activity exhibited by monoterpenes and their derivatives, including analgesic, anti-inflammatory, anticonvulsant, antidepressant, anti-Alzheimer, anti-Parkinsonian, antiviral, and antibacterial (anti-tuberculosis) effects. Searching for novel potential drugs among monoterpene derivatives shows great promise for treating various pathologies. Special attention is paid to the effect of absolute configuration of monoterpenes and monoterpenoids on their activity.

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Structure and Absolute Configuration of the Ansamycin Antibiotic Awamycin

Australian Journal of Chemistry ◽

10.1071/ch9920309 ◽

1992 ◽

Vol 45 (1) ◽

pp. 309 ◽

Cited By ~ 4

Author(s):

AJ Herlt ◽

RW Rickards ◽

GB Robertson

Keyword(s):

Absolute Configuration ◽

Crystal Structure Analysis ◽

Biologically Active ◽

Monoclinic Space Group ◽

X Ray Diffraction ◽

Tertiary Structures ◽

X Ray ◽

Parameters Analysis ◽

Solvent Molecules ◽

Absolute Stereochemistry

The structure and absolute configuration (3) of the biologically active ansamycin antibiotic awarnycin have been determined from X-ray diffraction data recorded at 129 K. Crystals are monoclinic, space group P2′2′2′, with a 25.426(3), b 30.823(2), c 13.592(1) A, and contain two molecules of the antibiotic and eleven solvent molecules (two water and nine ethanol) in each asymmetric scattering unit. The structure was solved with SHELXS and refined by full-matrix least-squares analysis to R 0.076 ( Rw 0.090) for 7308 reflections and 1174 refined parameters. Analysis of observed and calculated Bijvoet differences with the statistic Χ2 defines the absolute configuration of awamycin as 20R,21R,22R,23R,24R,25R,26R,27S,28S and the helicity as P. This is the first crystal structure analysis of an underivatized ansamycin antibiotic of the subgroup possessing an 18-membered ansa chain, and the first such analysisof an underivatized ansarnycin antibiotic in which it has been possible to assign absolute stereochemistry by the Bijvoet method. The constitution and absolute configuration of awamycin are compared with those of related ansarnycins carrying 18- and 19-membered ansa chains, and the tertiary structures of awarnycin and of several rifamycins and variants are analysed in relation to the arrangement of oxygen functions required for antibiotic activity.

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Absolute configuration of the alkaloid cularine: an X-ray structure determination

Journal of the Chemical Society Chemical Communications ◽

10.1039/c3972001072b ◽

1972 ◽

pp. 1072b ◽

Cited By ~ 5

Author(s):

T. Kametani ◽

T. Honda ◽

H. Shimanouchi ◽

Y. Sasada

Keyword(s):

Absolute Configuration ◽

Structure Determination ◽

X Ray

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Cannabidiol revisited

IUCrData ◽

10.1107/s2414314617002760 ◽

2017 ◽

Vol 2 (2) ◽

Cited By ~ 1

Author(s):

Tobias Mayr ◽

Tobias Grassl ◽

Nikolaus Korber ◽

Volker Christoffel ◽

Michael Bodensteiner

Keyword(s):

Absolute Configuration ◽

Structure Determination ◽

High Quality ◽

Acta Cryst ◽

X Ray ◽

Radiation Sources ◽

Wavelength Radiation ◽

The Absolute ◽

Absolute Structure ◽

Intensity Radiation

The crystal structure of cannabidiol, C21H30O2, {systematic name: 2-[(1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-enyl]-5-pentylbenzene-1,3-diol}, was determined earlier by Joneset al.[(1977).Acta Cryst.B33, 3211–3214] and Ottersen & Rosenqvist [(1977).Acta Chem. Scand.B31, 749–755]. In both investigations, the absolute configuration is given asR,R, referring to Mechoulamet al.[(1967.J. Am. Chem. Soc.89, 4552–4554]. In the latter, the absolute configuration was identified by chemical means. Using the advantages of modern single-crystal X-ray diffractometers such as area detectors and high-intensity radiation sources, a high-quality structure determination including the absolute configuration was possible and is shown in this work. Furthermore, the rather uncommon CuKβ wavelength radiation was applied for the structure determination, which confirmed the absolute structure to beR,R.

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Structural studies of P-type ATPase–ligand complexes using an X-ray free-electron laser

IUCrJ ◽

10.1107/s2052252515008969 ◽

2015 ◽

Vol 2 (4) ◽

pp. 409-420 ◽

Cited By ~ 17

Author(s):

Maike Bublitz ◽

Karol Nass ◽

Nikolaj D. Drachmann ◽

Anders J. Markvardsen ◽

Matthias J. Gutmann ◽

...

Keyword(s):

Membrane Proteins ◽

Structure Determination ◽

Free Electron ◽

Free Electron Laser ◽

Molecular Mechanisms ◽

Structural Information ◽

Biologically Active ◽

Atpase Inhibitor ◽

X Ray ◽

P Type

Membrane proteins are key players in biological systems, mediating signalling events and the specific transport ofe.g.ions and metabolites. Consequently, membrane proteins are targeted by a large number of currently approved drugs. Understanding their functions and molecular mechanisms is greatly dependent on structural information, not least on complexes with functionally or medically important ligands. Structure determination, however, is hampered by the difficulty of obtaining well diffracting, macroscopic crystals. Here, the feasibility of X-ray free-electron-laser-based serial femtosecond crystallography (SFX) for the structure determination of membrane protein–ligand complexes using microcrystals of various native-source and recombinant P-type ATPase complexes is demonstrated. The data reveal the binding sites of a variety of ligands, including lipids and inhibitors such as the hallmark P-type ATPase inhibitor orthovanadate. By analyzing the resolution dependence of ligand densities and overall model qualities, SFX data quality metrics as well as suitable refinement procedures are discussed. Even at relatively low resolution and multiplicity, the identification of ligands can be demonstrated. This makes SFX a useful tool for ligand screening and thus for unravelling the molecular mechanisms of biologically active proteins.

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Secondary Metabolites with α-Glucosidase Inhibitory Activity from the Mangrove Fungus Mycosphaerella sp. SYSU-DZG01

Marine Drugs ◽

10.3390/md17080483 ◽

2019 ◽

Vol 17 (8) ◽

pp. 483 ◽

Cited By ~ 3

Author(s):

Pei Qiu ◽

Zhaoming Liu ◽

Yan Chen ◽

Runlin Cai ◽

Guangying Chen ◽

...

Keyword(s):

Antioxidant Activity ◽

Secondary Metabolites ◽

Single Crystal ◽

Absolute Configuration ◽

Inhibitory Activity ◽

Spectroscopic Data ◽

X Ray Diffraction ◽

X Ray ◽

Ic50 Values ◽

New Metabolites

Four new metabolites, asperchalasine I (1), dibefurin B (2) and two epicoccine derivatives (3 and 4), together with seven known compounds (5–11) were isolated from a mangrove fungus Mycosphaerella sp. SYSU-DZG01. The structures of compounds 1–4 were established from extensive spectroscopic data and HRESIMS analysis. The absolute configuration of 1 was deduced by comparison of ECD data with that of a known structure. The stereostructures of 2–4 were further confirmed by single-crystal X-ray diffraction. Compounds 1, 8 and 9 exhibited significant α-glucosidase inhibitory activity with IC50 values of 17.1, 26.7 and 15.7 μM, respectively. Compounds 1, 4, 6 and 8 showed antioxidant activity by scavenging DPPH· with EC50 values ranging from 16.3 to 85.8 μM.

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A new perspective on fungal metabolites: identification of bioactive compounds from fungi using zebrafish embryogenesis as read-out

Scientific Reports ◽

10.1038/s41598-019-54127-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Jelmer Hoeksma ◽

Tim Misset ◽

Christie Wever ◽

Johan Kemmink ◽

John Kruijtzer ◽

...

Keyword(s):

Biological Activity ◽

Secondary Metabolites ◽

High Resolution Mass Spectrometry ◽

Biologically Active Compounds ◽

Biologically Active ◽

Therapeutic Drug ◽

Preparative Hplc ◽

Active Compounds ◽

Vis Spectroscopy ◽

Therapeutic Compounds

AbstractThere is a constant need for new therapeutic compounds. Fungi have proven to be an excellent, but underexplored source for biologically active compounds with therapeutic potential. Here, we combine mycology, embryology and chemistry by testing secondary metabolites from more than 10,000 species of fungi for biological activity using developing zebrafish (Danio rerio) embryos. Zebrafish development is an excellent model for high-throughput screening. Development is rapid, multiple cell types are assessed simultaneously and embryos are available in high numbers. We found that 1,526 fungal strains produced secondary metabolites with biological activity in the zebrafish bioassay. The active compounds from 39 selected fungi were purified by liquid-liquid extraction and preparative HPLC. 34 compounds were identified by a combination of chemical analyses, including LCMS, UV-Vis spectroscopy/ spectrophotometry, high resolution mass spectrometry and NMR. Our results demonstrate that fungi express a wide variety of biologically active compounds, consisting of both known therapeutic compounds as well as relatively unexplored compounds. Understanding their biological activity in zebrafish may provide insight into underlying biological processes as well as mode of action. Together, this information may provide the first step towards lead compound development for therapeutic drug development.

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