scholarly journals Ring D-Modified and Highly Reduced Angucyclinones From Marine Sediment-Derived Streptomyces sp.

2021 ◽  
Vol 9 ◽  
Author(s):  
Lin Guo ◽  
Qiaoli Yang ◽  
Guangfei Wang ◽  
Shumin Zhang ◽  
Ming Liu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Natural Products ◽  
Positive Control ◽  
Ring System ◽  
Antibiotic Activity ◽  
Type Ii ◽  
New Members ◽  
Streptomyces Sp ◽  
X Ray ◽  
X Ray Crystallography

Angucyclines and angucyclinones represent the largest family of type II PKS-engineered natural products. Chemical analysis of a marine Streptomyces sp. KCB-132 yielded three new members, actetrophenone A (1) and actetrophenols A–B (2–3). Their structures were elucidated by NMR spectroscopy, X-ray crystallography and CD calculations. Actetrophenone A (1) is the first representative of a novel-type angucyclinone bearing a nonaromatic D-ring. Actetrophenol A (2) features a highly reduced and aromatized four-ring system, which is unprecedented for natural products. While (Ra)- and (Sa)-actetrophenol B (3) bear an unprecedented N-acetyltryptamine-substituted tetraphene core skeleton, this is the first report of a pair of atropisomeric isomers in the angucyclinone family. Actetrophenol A (2) exhibits remarkable antibiotic activity, notably including potent activity to multiple resistant Staphylococcus aureus and Enterococcus faecium with MIC values of 4 μg/ml, in contrast, the positive control antimicrobial agent penicillin was inactive up to 32 μg/ml.

Tele-Substitution Reactions in the Synthesis of a Promising Class of Antimalarials

2020 ◽  
Author(s):  
Marat Korsik ◽  
Edwin Tse ◽  
David Smith ◽  
William Lewis ◽  
Peter J. Rutledge ◽  
...  
Keyword(s):  
Heterocyclic Ring ◽  
Ring System ◽  
Substitution Reactions ◽  
Laboratory Notebook ◽  
Polar Solvents ◽  
X Ray ◽  
X Ray Crystallography ◽  
The Core ◽  
Nmr Data

<p></p><p>We have discovered and studied a <i>tele</i>substitution reaction in a biologically important heterocyclic ring system. Conditions that favour the <i>tele</i>-substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base, or the use of softer nucleophiles, less polar solvents and larger halogens on the electrophile. Using results from X-ray crystallography and isotope labelling experiments a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the <i>in vivo </i>active anti-plasmodium compounds of Series 4 of the Open Source Malaria consortium.</p> <p> </p> <p>Archive of the electronic laboratory notebook with the description of all conducted experiments and raw NMR data could be accessed via following link <a href="https://ses.library.usyd.edu.au/handle/2123/21890">https://ses.library.usyd.edu.au/handle/2123/21890</a> . For navigation between entries of laboratory notebook please use file "Strings for compounds in the article.pdf" that works as a reference between article codes and notebook codes, also this file contain SMILES for these compounds. </p><br><p></p>

Preparation, Characterisation, Crystal Structure and Antibacterial Activity of two Bis-Schiff Bases Containing a Piperazine Ring

2018 ◽  
Vol 42 (10) ◽  
pp. 512-514
Author(s):  
Rui-bo Xu ◽  
Xiao-tian Yang ◽  
Hai-nan Li ◽  
Peng-cheng Zhao ◽  
Jiao-jiao Li ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Bacillus Subtilis ◽  
Schiff Bases ◽  
Piperazine Ring ◽  
X Ray ◽  
X Ray Crystallography ◽  
Good Antibacterial Activity

Two new bis-Schiff bases containing a piperazine ring, N,N‘-bis(4-chlorobenzylidene)- and N,N‘-bis(4-cyanobenzylidene)-1,4-bis(3-aminopropyl)piperazine, were prepared by the reaction of N,N‘-bis(3-aminopropyl)piperazine with 4-chloro- and 4-cyanobenzaldehyde, respectively. The dichloro compound was fully identified by X-ray crystallography and it exhibited good antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis.

scholarly journals Structural insight into the Staphylococcus aureus ATP-driven exporter of virulent peptide toxins

2020 ◽  
Vol 6 (40) ◽  
pp. eabb8219
Author(s):  
N. Zeytuni ◽  
S. W. Dickey ◽  
J. Hu ◽  
H. T. Chou ◽  
L. J. Worrall ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bound State ◽  
Broad Spectrum Antibiotic ◽  
X Ray ◽  
X Ray Crystallography ◽  
Open Conformation ◽  
Mechanistic Insight ◽  
Cytolytic Peptides ◽  
Peptide Toxins ◽  
Insight Into

Staphylococcus aureus is a major human pathogen that has acquired alarming broad-spectrum antibiotic resistance. One group of secreted toxins with key roles during infection is the phenol-soluble modulins (PSMs). PSMs are amphipathic, membrane-destructive cytolytic peptides that are exported to the host-cell environment by a designated adenosine 5′-triphosphate (ATP)–binding cassette (ABC) transporter, the PSM transporter (PmtABCD). Here, we demonstrate that the minimal Pmt unit necessary for PSM export is PmtCD and provide its first atomic characterization by single-particle cryo-EM and x-ray crystallography. We have captured the transporter in the ATP-bound state at near atomic resolution, revealing a type II ABC exporter fold, with an additional cytosolic domain. Comparison to a lower-resolution nucleotide-free map displaying an “open” conformation and putative hydrophobic inner chamber of a size able to accommodate the binding of two PSM peptides provides mechanistic insight and sets the foundation for therapeutic design.

scholarly journals Constrained Dipeptide Surrogates: 5- and 7-Hydroxy Indolizidin-2-one Amino Acid Synthesis from Iodolactonization of Dehydro-2,8-diamino Azelates

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 67
Author(s):  
Ramakotaiah Mulamreddy ◽  
William D. Lubell
Keyword(s):  
Amino Acids ◽  
Acid Synthesis ◽  
Ring System ◽  
Dihedral Angles ◽  
Type Ii ◽  
Amino Ester ◽  
Amino Acid Synthesis ◽  
X Ray ◽  
Amino Esters ◽  
Peptide Mimicry

The constrained dipeptide surrogates 5- and 7-hydroxy indolizidin-2-one N-(Boc)amino acids have been synthesized from L-serine as a chiral educt. A linear precursor ∆4-unsaturated (2S,8S)-2,8-bis[N-(Boc)amino]azelic acid was prepared in five steps from L-serine. Although epoxidation and dihydroxylation pathways gave mixtures of hydroxy indolizidin-2-one diastereomers, iodolactonization of the ∆4-azelate stereoselectively delivered a lactone iodide from which separable (5S)- and (7S)-hydroxy indolizidin-2-one N-(Boc)amino esters were synthesized by sequences featuring intramolecular iodide displacement and lactam formation. X-ray analysis of the (7S)-hydroxy indolizidin-2-one N-(Boc)amino ester indicated that the backbone dihedral angles embedded in the bicyclic ring system resembled those of the central residues of an ideal type II’ β-turn indicating the potential for peptide mimicry.

scholarly journals Conformational investigation of alpha,beta-dehydropeptides. XIII. Conformational properties of N-acetyl-alpha,beta-dehydrovaline N',N'-dimethylamide.

2004 ◽  
Vol 51 (1) ◽  
pp. 145-152 ◽  
Author(s):  
Dawid Siodłak ◽  
Barbara Rzeszotarska ◽  
Małgorzata A Broda ◽  
Anna E Kozioł ◽  
Edyta Kołodziejczyk
Keyword(s):  
Type Ii ◽  
Beta Turn ◽  
X Ray ◽  
X Ray Crystallography ◽  
Tertiary Amide ◽  
Conformational Investigation ◽  
Conformational Properties ◽  
Alpha Beta ◽  
Solid State Conformation ◽  
Ab Initio Dft

The crystal structure of Ac-DeltaVal-NMe(2) (DeltaVal = alpha,beta-dehydrovaline) was determined by X-ray crystallography. The found angles phi = -60 degrees and psi = 125 degrees correspond exactly to the respective values of the (i + 1)th residue in idealised beta-turn II/VIa. Ab initio/DFT studies revealed that the molecule adopts the angle psi restricted only to about |130 degrees | and very readily attains the angle phi = about -50 degrees. This is in line with its solid-state conformation. Taken together, these data suggest that the DeltaVal residue combined with a C-terminal tertiary amide is a good candidate at the (i + 1)th position in a type II/VIa beta-turn.

scholarly journals The canal inclusion complex of allicin with carbamide: Preparation, characterization and microbiological investigation

2005 ◽  
Vol 11 (2) ◽  
pp. 69-73 ◽  
Author(s):  
Vesna Nikolic ◽  
Mihajlo Stankovic ◽  
Ljubisa Nikolic ◽  
Dragan Cvetkovic ◽  
Agnes Kapor ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Candida Albicans ◽  
Inclusion Complex ◽  
Microbiological Investigation ◽  
X Ray ◽  
X Ray Crystallography ◽  
Bacteria And Fungi ◽  
Growth Of Bacteria

The carbamide:allicin canal inclusion complex was prepared in the solid state. The structure of the complex obtained was characterized by x-ray crystallography, infrared spectroscopy and thermogravimetric analysis. The microbiological activities of the inclusion complex and allicin were investigated and compared with respect to fungi (Candida albicans ATCC 10231 and Aspergillus niger ATCC 16404) and bacteria (Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027). It was found that the inclusion complex inhibited the growth of bacteria and fungi for a longer period than allicin in the free state.

scholarly journals Modulation of the Antibiotic Activity by Extracts fromAmburana cearensisA. C. Smith andAnadenanthera macrocarpa(Benth.) Brenan

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Fernando G. Figueredo ◽  
Emerson O. Ferreira ◽  
Bruno F. F. Lucena ◽  
Cícero M. G. Torres ◽  
Daniel L. Lucetti ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Natural Products ◽  
Inhibitory Concentration ◽  
Antibiotic Activity ◽  
Subinhibitory Concentration ◽  
Antimicrobial Drugs ◽  
Ethanol Extracts ◽  
Multiresistant Strains

The aim of this study was to verify the possible interactions between ethanol extracts ofAmburana cearensisA. C. Smith andAnadenanthera macrocarpa(Benth.) Brenan, combined with six antimicrobial drugs against multiresistant strains ofStaphylococcus aureusandEscherichia coliisolated from humans. The antibacterial activity of the extracts was determined using the minimum inhibitory concentration (MIC). The microdilution assay was performed to verify the interactions between the natural products and the antibiotics using a subinhibitory concentration. The activity of amikacin associated with the extract ofAnadenanthera macrocarpaagainst EC 27 was enhanced, demonstrating an MIC reduction from 128 to 4 μg/mL. Among theβ-lactams, no potentiation on its activity was observed, with exception to the antagonism of the natural products with ampicillin againstS. aureus358.

scholarly journals X-Ray crystallography and the chemistry of the steroids. Part I

1940 ◽  
Vol 239 (802) ◽  
pp. 135-182 ◽  
Keyword(s):  
Crystal Morphology ◽  
Ring System ◽  
Higher Plant ◽  
X Ray ◽  
X Ray Crystallography ◽  
Unit Cell Size ◽  
Molecular Arrangement ◽  
Preliminary Examination ◽  
Optic Orientation ◽  
Shape And Size

A survey has been made of the X-ray crystallography of some eighty sterol derivatives belonging mainly to the cholesterol and ergosterol series but including also calciferol and other photoderivatives of ergosterol and some higher plant and animal sterols. The measurements are recorded in four tables and include determinations of unit cell size, space group and some data on the crystal morphology and optics. In three cases, cholesteryl chloride, bromide and cholesteryl chloride hydrochloride, Patterson projections have also been derived from the intensities of the X-ray reflexions of the hOl planes. These confirm earlier deductions on the shape and size of the sterol molecules, proving that these are roughly lath-shaped, 20 x 7 x 4 A, and the details of the patterns can also to some degree be correlated with the actual arrangement of the carbon atoms in the sterol ring system and with the positions of the chlorine and bromine atoms. The arrangement of the molecules in the crystal units is closely that given by the preliminary examination from the optic orientation, and this has therefore been employed to suggest in each of the remaining sterol crystal structures the probable molecular arrangement

scholarly journals Discovery of the Antibiotic Polyketide Tatiomicin via a Genomics Guided Analysis of Amycolatopsis sp. DEM30355

2020 ◽  
Author(s):  
Bernhard Kepplinger ◽  
Joseph Cowell ◽  
Stephanie Morton-Laing ◽  
Corinne Wills ◽  
Emma Marrs ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Natural Products ◽  
Computational Methods ◽  
Antibiotic Activity ◽  
Structural Elucidation ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Stereochemical Assignment ◽  
Bioactive Natural Products ◽  
Gram Positive Bacteria

The application of genomic techniques to the investigation of understudied species of actinobacteria provides an expedited route to the discovery of new bioactive natural products. We report the isolation of the antibiotic polyketide tatiomicin, through a genomics and bioactivity informed analysis of the metabolome of the extremophile <i>Amycolatopsis</i> sp. DEM30355. Structural elucidation including absolute stereochemical assignment was performed using complementary crystallographic, spectroscopic and computational methods. Tatiomicin shows antibiotic activity against Gram-positive bacteria, including Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).

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