scholarly journals Proteins as possible targets for antitumor metal complexes: biophysical studies of their interactions

2009 ◽  
Author(s):  
Chiara Gabbiani
Keyword(s):  
Mechanism Of Action ◽  
Anticancer Agents ◽  
Protein Adducts ◽  
Functional Information ◽  
X Ray Diffraction ◽  
Protein Targets ◽  
X Ray ◽  
Important Group ◽  
Biophysical Studies ◽  
Anticancer Metallodrugs

There is considerable interest today for the reactions of anticancer metallodrugs with proteins as these interactions might feature processes that are crucial for the biodistribution, the toxicity and even the mechanism of action of this important group of anticancer agents. Valuable structural and functional information on these adducts could be derived from several biophysical studies mainly relying on the application of X-ray diffraction and ESI MS techniques. The structural and functional information achieved on the respective metallodrug–protein adducts allowed us to identify some general trends in the reactivity of anticancer metallodrugs with protein targets.

scholarly journals Metalloproteomics for molecular target identification of protein-binding anticancer metallodrugs

Metallomics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1627-1636
Author(s):  
Tasha R. Steel ◽  
Christian G. Hartinger
Keyword(s):  
Protein Binding ◽  
Anticancer Agents ◽  
Target Identification ◽  
Molecular Target ◽  
Protein Targets ◽  
Anticancer Metallodrugs

The development of the metallodrug pull-down as a metalloproteomic technique has enabled the identification of the protein targets of metal-based anticancer agents.

Anti-amoebic Activity of Leaf Extracts and Aporphine Alkaloids Obtained from Annona purpurea

Planta Medica ◽  
2020 ◽  
Vol 86 (06) ◽  
pp. 425-433 ◽  
Author(s):  
César Díaz-Godínez ◽  
Julio C. Ontiveros-Rodríguez ◽  
Diana G. Ríos-Valencia ◽  
José Enrique Herbert-Pucheta ◽  
L. Gerardo Zepeda-Vallejo ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Morphological Changes ◽  
Annexin V ◽  
Socioeconomically Disadvantaged ◽  
X Ray Diffraction ◽  
Leaf Extracts ◽  
1H And 13C Nmr ◽  
X Ray ◽  
Dye Reduction ◽  
First Time

Abstract Annona purpurea has been traditionally used by indigenous and socioeconomically disadvantaged people to treat infectious and parasitic diseases, including amoebiasis. The goal of this study was to assess the effect of a crude methanolic extract, an alkaloid extract, and aporphine alkaloids from leaves of A. purpurea on the viability of Entamoeba histolytica trophozoite cultures and to identify the mechanism of action. Different concentrations of the extracts and alkaloids purpureine (1), 3-hydroxyglaucine (2), norpurpureine (3) glaziovine (4), and oxopurpureine (5) were added to the cultures, and dead parasites were counted after 24 h using a tetrazolium dye reduction assay and analyzed by flow cytometry. The crude extract did not affect the viability of amoebae, but the alkaloid extract and the derived alkaloid glaziovine (4) had important anti-amoebic activity with an IC50 of 33.5 µM compared to that shown by metronidazole (6.8 µM). The treatments induced significant morphological changes in the trophozoites, and most parasites killed by the alkaloid extract were positive for Annexin V, suggesting that apoptosis was the main mechanism of action. In contrast, glaziovine (4) induced less apoptosis with more amoebic lysis. This study supports the idea that aporphine alkaloids from A. purpurea, mainly (+)-(R)-glaziovine (4), could contribute to the development of new formulations for the treatment of amoebiasis. In addition, X-ray diffraction structural analysis and complete 1H and 13C NMR assignments of (+)-(R)-glaziovine (4) were performed and reported for the first time.

scholarly journals SYNTHESIS, CRYSTAL STUDIES AND PHARMACOLOGICAL ROLE PREDICTION OF 3-IODO-2- METHYL-1 PHENYL SULFONYL-1H INDOLE

2017 ◽  
Vol 10 (3) ◽  
pp. 341
Author(s):  
C Rama Thilagam ◽  
S Vijaya Sri ◽  
Waheeta Hopper ◽  
V Mani Vannan ◽  
P.r Uma Rani
Keyword(s):  
Single Crystal ◽  
Binding Energies ◽  
Amino Acid Residues ◽  
X Ray Diffraction ◽  
Protein Targets ◽  
X Ray ◽  
Raf Kinase ◽  
Starting Compound ◽  
Docking Method ◽  
Wet Lab

ABSTRACTObjective: Indole-based compounds have established many pharmacological applications. Indole acts as a starting compound for various medicinalpreparations. Our objective is to determine the possible pharmacological roles of our crystallized indole-based ligand using computational approach.The activities studied are antibacterial, antitubercular, and antimelanoma.Methods: The structure of the indole compound, CR2 was studied using single crystal X-ray diffraction technique. To predict the pharmacologicalactivities, the structure-based docking method was followed. The protein targets were selected based on their important biological role in eachactivity mentioned above. The interactions between the targets and the crystal ligand were studied using a generic based docking algorithm. Thesignificant pharmacophore features of the ligand were also reported.Results: The ligand showed bonded and non-bonded interactions with the crucial amino acid residues of the active site of each target. The interactionsand the binding energies were quite comparable to the targets’ natural ligands.Conclusion: We suggest through the computational approaches that the ligand may have antitubercular, antibacterial, and antimelanoma activitieswith respect to the targets considered. The new insights of this compound as predicted by the computational methods are believed to provide aplatform for the futuristic pharmacological activities of this compound that can be further considered for wet lab techniques.Keywords: Indole, Dihydrofolate reductase, DNA gyrase, Human B-Raf kinase, Docking, Pharmacophore, Single crystal X-ray diffraction.

scholarly journals In celluloserial crystallography of alcohol oxidase crystals inside yeast cells

IUCrJ ◽  
2016 ◽  
Vol 3 (2) ◽  
pp. 88-95 ◽  
Author(s):  
Arjen J. Jakobi ◽  
Daniel M. Passon ◽  
Kèvin Knoops ◽  
Francesco Stellato ◽  
Mengning Liang ◽  
...  
Keyword(s):  
Diffraction Data ◽  
Hansenula Polymorpha ◽  
Alcohol Oxidase ◽  
Methylotrophic Yeast ◽  
Yeast Cells ◽  
Powder Diffraction Data ◽  
X Ray Diffraction ◽  
Protein Targets ◽  
X Ray ◽  
Serial Crystallography

The possibility of using femtosecond pulses from an X-ray free-electron laser to collect diffraction data from protein crystals formed in their native cellular organelle has been explored. X-ray diffraction of submicrometre-sized alcohol oxidase crystals formed in peroxisomes within cells of genetically modified variants of the methylotrophic yeastHansenula polymorphais reported and characterized. The observations are supported by synchrotron radiation-based powder diffraction data and electron microscopy. Based on these findings, the concept ofin celluloserial crystallography on protein targets imported into yeast peroxisomes without the need for protein purification as a requirement for subsequent crystallization is outlined.

scholarly journals Structure of N-(3,4-Dimethoxyphenyl)pyrido[3′,2′:4,5]-thieno[3,2-d]pyrimidin-4-amine, a New Inhibitor of CLK1 and DYRK1A Kinases

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Jean Guillon ◽  
Mathieu Marchivie ◽  
Yvonnick Loidreau ◽  
Noël Pinaud ◽  
Thierry Besson
Keyword(s):  
Crystal Structure ◽  
Solid State ◽  
Single Crystal ◽  
Mechanism Of Action ◽  
Biological Mechanism ◽  
X Ray Diffraction ◽  
Dimroth Rearrangement ◽  
Orthorhombic Space Group ◽  
State Data ◽  
X Ray

The complete crystal structure of N-(3,4-dimethoxyphenyl)pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-amine, synthesized via a Dimroth rearrangement and designed as new inhibitor of CLK1 and DYRK1A kinases, was established by a single-crystal X-ray diffraction. The crystal is orthorhombic, space group Pca21; a = 13.1593  (9), b = 13.9823  (10), c=8.5403  (7) Å, α=β=γ=90°, V = 1571.4  (2)  Å3, and Z=4, C17H14N4O2S. Solid-state data could be used to enlighten the biological mechanism of action.

Design and in vitro biological evaluation of substituted chalcones synthesized from nitrogen mustards as potent microtubule targeted anticancer agents

2017 ◽  
Vol 41 (10) ◽  
pp. 4096-4109 ◽  
Author(s):  
X. Janet Sabina ◽  
J. Karthikeyan ◽  
Gunasekaran Velmurugan ◽  
M. Muthu Tamizh ◽  
A. Nityananda Shetty
Keyword(s):  
Single Crystal ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
X Ray Diffraction ◽  
Nitrogen Mustards ◽  
X Ray

Six chalcones were synthesized and their structures determined by single crystal X-ray diffraction studies. They exhibited enhanced anticancer activity and tubulin inhibition.

scholarly journals Synthesis and crystal structure of cytotoxic copper(II) complex with 1,10-phenanthroline-5,6-dione and isothiazole derivative

2022 ◽  
Vol 11 (4) ◽  
pp. 531-539
Author(s):  
Yu. A. Golubeva ◽  
K. S. Smirnova ◽  
L. S. Klyushova ◽  
V. I. Potkin ◽  
E. V. Lider
Keyword(s):  
Ir Spectroscopy ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Diffraction Data ◽  
Density Functional ◽  
Breast Adenocarcinoma ◽  
High Dose ◽  
X Ray Diffraction ◽  
X Ray

Oligopyridine based copper(II) complexes are of interest to scientists as possible anticancer agents due to promising cytotoxic and DNA binding/cleaving properties. In this study, copper(II) complex [Cu(phendione)L2]·C2H5OH with 1,10-phenanthroline-5,6-dione (phendione) and 4,5-dichloro-isothiazole-3-carboxylic acid (HL) was synthesized and characterized by elemental analysis, IR-spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. According to X-ray diffraction data, obtained compound is mononuclear complex with square pyramidal coordination environment of the central atom which is surrounded by two isothiazolate molecules and one phendione ligand. The X-ray diffraction data are confirmed by IR-spectroscopy data showing the presence of characteristic stretching vibration bands of the carbonyl and carboxyl groups of oligopyridine ligand and isothiazolate ions, respectively. Density functional theory (DFT) calculations for complex were carried out using the ADF software package to perform geometry optimization and frequency calculations that were in a good agreement with experimental IR spectrum. Cytotoxicity of complex and initial reagents was tested in vitro against HepG2 (human hepatocellular carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines. The complex showed high dose-dependent cytotoxic activity with the IC50 values of 0.60±0.03 µM and 0.96±0.13 µM, respectively, which is higher than the activity of cisplatin against these cell lines. The activity of the complex is due to the presence of phendione ligand, which exhibits a similar cytotoxic activity.

The Use of Advanced Analytical Techniques for Characterization of the Chemical, Physical, and Crystallographic Nature of a Surface

1973 ◽  
Vol 31 ◽  
pp. 132-133 ◽  
Author(s):  
R. E. Herfert
Keyword(s):  
Surface Characterization ◽  
Analytical Techniques ◽  
X Ray Diffraction ◽  
Depth Of Penetration ◽  
X Ray ◽  
The Past ◽  
Transmission Electron ◽  
Scanning Electron

Studies of the nature of a surface, either metallic or nonmetallic, in the past, have been limited to the instrumentation available for these measurements. In the past, optical microscopy, replica transmission electron microscopy, electron or X-ray diffraction and optical or X-ray spectroscopy have provided the means of surface characterization. Actually, some of these techniques are not purely surface; the depth of penetration may be a few thousands of an inch. Within the last five years, instrumentation has been made available which now makes it practical for use to study the outer few 100A of layers and characterize it completely from a chemical, physical, and crystallographic standpoint. The scanning electron microscope (SEM) provides a means of viewing the surface of a material in situ to magnifications as high as 250,000X.

Ribosome Structural Organization

1974 ◽  
Vol 32 ◽  
pp. 332-333
Author(s):  
James A. Lake
Keyword(s):  
Ribosomal Proteins ◽  
Structural Organization ◽  
Three Dimensional ◽  
Small Subunit ◽  
Structural Studies ◽  
X Ray Diffraction ◽  
Specific Antibodies ◽  
X Ray ◽  
E Coli ◽  
Complete Sequences

The understanding of ribosome structure has advanced considerably in the last several years. Biochemists have characterized the constituent proteins and rRNA's of ribosomes. Complete sequences have been determined for some ribosomal proteins and specific antibodies have been prepared against all E. coli small subunit proteins. In addition, a number of naturally occuring systems of three dimensional ribosome crystals which are suitable for structural studies have been observed in eukaryotes. Although the crystals are, in general, too small for X-ray diffraction, their size is ideal for electron microscopy.

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