scholarly journals A Molecular Dynamics Study of a Photodynamic Sensitizer for Cancer Cells: Inclusion Complexes of γ-Cyclodextrins with C70

2019 ◽  
Vol 20 (19) ◽  
pp. 4831 ◽  
Author(s):  
Giuseppina Raffaini ◽  
Fabio Ganazzoli
Keyword(s):  
Molecular Dynamics ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Inclusion Complexes ◽  
Direct Injection ◽  
Theoretical Work ◽  
Stable Complex ◽  
Apolar Solvent ◽  
Molecular Dynamics Methods ◽  
The Stability

Photodynamic therapy is an emerging treatment of tumor diseases. The complexes with γ-cyclodextrins (γ-CD) and fullerenes or their derivatives can be used as photosensitizers by direct injection into cancer cells. Using molecular mechanics and molecular dynamics methods, the stability and the geometry of the 2:1 complexes [(γ-CD)2/C70] are investigated analyzing the differences with the analogous C60 complexes, studied in a previous theoretical work and experimentally found to be much less efficient in cancer therapy. The inclusion complex of γ-CD and C70 has a 2:1 stoichiometry, the same as C60, but is significantly less stable and displays an unlike arrangement. In vacuo, mimicking an apolar solvent, the complex is compact, whereas in water the two γ-CDs encapsulate C70 forming a relatively stable complex by interacting through their primary rims, however exposing part of C70 to the solvent. Other higher-energy complexes with the γ-CDs facing different rims can form in water, but in all cases part of the hydrophobic C70 surface remains exposed to water. The stability and arrangement of these peculiar amphiphilic inclusion complexes having non-covalent interactions in water can be an important key for cancer therapy to enhance both the solubilization and the fullerene insertion into liposomes or cell membranes.

scholarly journals Interaction of Coumarin Phytoestrogens with ERα and ERβ: A Molecular Dynamics Simulation Study

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1165 ◽  
Author(s):  
Ting Wang ◽  
Yunfei Wang ◽  
Xuming Zhuang ◽  
Feng Luan ◽  
Chunyan Zhao ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Binding Free Energy ◽  
Human Life ◽  
Simulation Method ◽  
Binding Mode ◽  
Dynamics Simulation ◽  
Molecular Dynamics Methods ◽  
17Β Estradiol ◽  
The Stability

Coumarin phytoestrogens, as one of the important classes of phytoestrogens, have been proved to play an important role in various fields of human life. In this study, molecular simulation method including molecular docking and molecular dynamics methods were performed to explore the various effects between four classical coumarin phytoestrogens (coumestrol, 4-methoxycoumestrol, psoralen and isopsoralen), and estrogen receptors (ERα, ERβ), respectively. The calculated results not only proved that the four coumarin phytoestrogens have weaker affinity than 17β-estradiol to both ERα, and ERβ, but also pointed out that the selective affinity for ERβ is greater than ERα. In addition, the binding mode indicated that the formation of hydrogen bond and hydrophobic interaction have an important effect on the stability of the complexes. Further, the calculation and decomposition of binding free energy explored the main contribution interactions to the total free energy.

Effect of Structural Variability of the Ceramide Part on the Saccharide-Ceramide Linkage in Model Glycolipids Studied by Molecular Mechanics and Molecular Dynamics Methods

1996 ◽  
Vol 61 (10) ◽  
pp. 1405-1431
Author(s):  
Zuzana Gálová ◽  
Tibor Kožár
Keyword(s):  
Molecular Dynamics ◽  
Molecular Mechanics ◽  
Energy Surface ◽  
Structural Parameters ◽  
Structural Variability ◽  
Molecular Dynamics Methods ◽  
Set Up ◽  
The Stability ◽  
Dynamics Simulations ◽  
Torsional Angles

Conformational analysis was performed for model glycosphingolipid molecules with a view to studying the effect of structural variability of the lipidic part and its flexibility on the saccharide-ceramide linkage. In addition to systematic and random molecular mechanics sampling techniques (the RAMM program), molecular dynamics simulations (Biosym DISCOVER program) were carried out to analyze the conformational energy surface of the model glycolipid molecules. The influence of the structural variability and flexibility of the lipidic part is demonstrated by prediction of the stability of different conformations around the carbohydrate-ceramide linkage. The α2, α1 and Θ1 torsional angles are the most important structural parameters with respect to the carbohydrate-ceramide connection. Two dominant conformations for the saccharide-ceramide linkage were observed, with the α2/α1/Θ1 dihedral angles in the -sc/+ac/ap and -sc/ap/-sc regions. While each of the calculation methods predicts similar flexibility in the α2/α1 space, the flexibility around the Θ1 angle differs considerably, reflecting the parametrization and set-up of the modelling protocol.

scholarly journals Titania Nanosheets Generates Peroxynitrite for S-Nitrosylation and Enhanced p53 Function in Lung Cancer Cells

2021 ◽  
Author(s):  
Rapeepun Soonnarong ◽  
Sucharat Tungsukruthai ◽  
Bodee Nutho ◽  
Thanyada Rungrotmongkol ◽  
Chanida Vinayanuwattikun ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Lung Cancer ◽  
Molecular Dynamics ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Mechanism Of Action ◽  
Lung Cancer Cells ◽  
Positive Staining ◽  
Apoptosis Induction ◽  
Normal Cells

Abstract Background: Metal oxide nanomaterials are increasingly being exploited in cancer therapy thanks to their unique properties, which can enhance the efficacy of current cancer therapies. However, the nanotoxicity and mechanism of Ti0.8O2 nanosheets for specific site-targeting strategies in NSCLC have not yet been investigated.Methods: The effects of Ti0.8O2 nanosheets on cytotoxicity in NSCLC cells and normal cells were examined. The apoptosis characteristics, including condensed and fragmented nuclei, as assessed by positive staining with annexin V. The cellular uptake of the nanosheets and the induction of stress fiber were assessed via transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses, respectively. We also evaluated the expression of protein in death mechanism to identify the molecular mechanisms behind the toxicity of these cells. We investigated the relationship between S-nitrosylation and the increase in p53 stability by molecular dynamics.Results: Ti0.8O2 nanosheets caused cytotoxicity in several lung cancer cells, but not in normal cells. The nanosheets could enter lung cancer cells and exert an apoptosis induction. Results for protein analysis further indicated the activation of p53, increased Bax, decreased Bcl-2 and Mcl-1, and activation of caspase-3. The nanosheets also exhibited a substantial apoptosis effect in drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than that of cisplatin and etoposide. In terms of their mechanism of action, we found that the mode of apoptosis induction was through the generation of cellular ONOO− mediated the S-nitrosylation of p53 at C182. Molecular dynamics analysis further showed that the S-nitrosylation of one C182 stabilized the p53 dimer. Consequently, this nitrosylation of the protein led to an upregulation of p53 through its stabilization.Conclusions: Taking all the evidence together, we provided information on the apoptosis induction effect of the nanosheets through a molecular mechanism involving reactive nitrogen species, which affects the protein stability; thus emphasizing the novel mechanism of action of nanomaterials for cancer therapy.

Integrating virtual screening and biochemical experimental approach to identify potential anti-cancer agents from drug databank

2018 ◽  
Vol 16 (03) ◽  
pp. 1850002
Author(s):  
Suman Jyoti Deka ◽  
Ashalata Roy ◽  
Debasis Manna ◽  
Vishal Trivedi
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Virtual Screening ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mitochondrial Pathway ◽  
Dynamics Simulation ◽  
Stable Complex ◽  
C2 Domain ◽  
Anti Cancer

Chemical libraries constitute a reservoir of pharmacophoric molecules to identify potent anti-cancer agents. Virtual screening of heterocyclic compound library in conjugation with the agonist-competition assay, toxicity-carcinogenicity analysis, and string-based structural searches enabled us to identify several drugs as potential anti-cancer agents targeting protein kinase C (PKC) as a target. Molecular modeling study indicates that Cinnarizine fits well within the PKC C2 domain and exhibits extensive interaction with the protein residues. Molecular dynamics simulation of PKC–Cinnarizine complex at different temperatures (300, 325, 350, 375, and 400[Formula: see text]K) confirms that Cinnarizine fits nicely into the C2 domain and forms a stable complex. The drug Cinnarizine was found to bind PKC with a dissociation constant Kd of [Formula: see text]M. The breast cancer cells stimulated with Cinnarizine causes translocation of PKC-[Formula: see text] to the plasma membrane as revealed by immunoblotting and immunofluorescence studies. Cinnarizine also dose dependently reduced the viability of MDAMB-231 and MCF-7 breast cancer cells with an IC[Formula: see text] of [Formula: see text] and [Formula: see text]g/mL, respectively. It is due to the disturbance of cell cycle of breast cancer cells with reduction of S-phase and accumulation of cells in G1-phase. It disturbs mitochondrial membrane potentials to release cytochrome C into the cytosol and activates caspase-3 to induce apoptosis in cancer cells. The cell death was due to induction of apoptosis involving mitochondrial pathway. Hence, the current study has assigned an additional role to Cinnarizine as an activator of PKC and potentials of the approach to identify new molecules for anti-cancer therapy. Thus, in silico screening along with biochemical experimentation is a robust approach to assign additional roles to the drugs present in the databank for anti-cancer therapy.

Molecular Dynamics Studies of Diamondlike Amorphous Carbon

1994 ◽  
Vol 336 ◽  
Author(s):  
P. A. Fedders ◽  
D. A. Drabold
Keyword(s):  
Molecular Dynamics ◽  
Amorphous Carbon ◽  
First Principles ◽  
Structural Models ◽  
Theoretical Work ◽  
Vibrational Properties ◽  
Defect States ◽  
Amorphous Network ◽  
Molecular Dynamics Methods ◽  
Compare And Contrast

ABSTRACTFirst principles molecular dynamics methods are used to construct supercells for diamondlike Amorphous carbon, to study its properties, and to compare and contrast it with a-Si. As with recent lab fabricated material, these supercells contain no hydrogen. Several structural models are introduced and the topological, electronic, and vibrational properties are discussed. In particular, in spite of the presence of 3-fold coordinated sites and no hydrogenation, we have obtained a supercell sample that has a gap of about 2.5 eV containing no defect states. To our knowledge, ours is the only theoretical work that agrees with recent experiments in this respect. We explore the nature of defects in the Amorphous network and, in particular, the atomistic origin of the clean gap in unhydrogenated C but not in unhydrogenated Si.

scholarly journals Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

2015 ◽  
Vol 11 ◽  
pp. 2459-2473 ◽  
Author(s):  
Giuseppina Raffaini ◽  
Antonino Mazzaglia ◽  
Fabio Ganazzoli
Keyword(s):  
Molecular Dynamics ◽  
Building Blocks ◽  
Dispersion Interactions ◽  
Nucleation Stage ◽  
Aggregation Behaviour ◽  
Apolar Solvent ◽  
Initial Nucleation ◽  
Molecular Dynamics Methods ◽  
Pharmaceutical Properties ◽  
Dynamics Simulations

Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a “bottom up” approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD), which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties.

scholarly journals Preparation and Characterization of Inclusion Complexes of β-Cyclodextrin and Phenolics from Wheat Bran by Combination of Experimental and Computational Techniques

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4275 ◽  
Author(s):  
Tuba Simsek ◽  
Bakhtiyor Rasulev ◽  
Christian Mayer ◽  
Senay Simsek
Keyword(s):  
Complex Formation ◽  
Inclusion Complexes ◽  
Phenolic Acids ◽  
Wheat Bran ◽  
Stable Complex ◽  
Computational Techniques ◽  
Qspr Model ◽  
Covalent Bonds ◽  
Wheat Bran Extract ◽  
The Stability

Bitterness often associated with whole wheat products may be related to phenolics in the bran. Cyclodextrins (CDs) are known to form inclusion complexes. The objective was to form inclusion complexes between β-CD and wheat phenolics. Pure phenolic acids (trans-ferulic acid (FA), caffeic acid (CA), and p-coumaric acid (CO)) and phenolic acids from wheat bran were used to investigate complex formation potential. Complexes were characterized by spectroscopy techniques, and a computational and molecular modeling study was carried out. The relative amount of complex formation between β-CD and wheat bran extract was CA > CO > FA. The phenolic compounds formed inclusion complexes with β-CDs by non-covalent bonds. The quantum-mechanical calculations supported the experimental results. The most stable complex was CO/β-CD complex. The ΔH value for CO/β-CD complex was −11.72 kcal/mol and was about 3 kcal/mol more stable than the other complexes. The QSPR model showed good correlation between binding energy and 1H NMR shift for the H5 signal. This research shows that phenolics and β-CD inclusion complexes could be utilized to improve the perception of whole meal food products since inclusion complexes have the potential to mask the bitter flavor and enhance the stability of the phenolics in wheat bran.

scholarly journals Metadynamics supports molecular dynamics simulation-based binding affinities of eucalyptol and beta-cyclodextrin inclusion complexes

RSC Advances ◽  
2017 ◽  
Vol 7 (80) ◽  
pp. 50899-50911 ◽  
Author(s):  
Bodee Nutho ◽  
Nadtanet Nunthaboot ◽  
Peter Wolschann ◽  
Nawee Kungwan ◽  
Thanyada Rungrotmongkol
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Inclusion Complexes ◽  
Dynamics Simulation ◽  
Binding Affinities ◽  
Cyclodextrin Inclusion Complexes ◽  
Beta Cyclodextrin ◽  
Cyclodextrin Inclusion ◽  
Simulation Based ◽  
Molecular Dynamics Methods

The development of various molecular dynamics methods enables the detailed investigation of association processes, like host–guest complexes, including their dynamics and, additionally, the release of the guest compound.

Instant 99mTc-Labelled Glucoheptonate Kit for Kidney Imaging

1983 ◽  
Vol 22 (05) ◽  
pp. 246-250 ◽  
Author(s):  
M. Al-Hilli ◽  
H. M. A. Karim ◽  
M. H. S. Al-Hissoni ◽  
M. N. Jassim ◽  
N. H. Agha
Keyword(s):  
Sodium Hydroxide Solution ◽  
Normal Subjects ◽  
Organ Distribution ◽  
Stable Complex ◽  
Scintillation Camera ◽  
Ph Adjustment ◽  
The Mean ◽  
The Stability ◽  
Kidney Imaging ◽  
Mean Concentration

Gelchromatography column scanning has been used to study the fractions of reduced hydrolyzed 99mTc, 99mTc-pertechnetate and 99mTc-chelate in a 99mTc-glucoheptonate (GH) preparation. A stable high labelling yield of 99mTc-GH complex in the radiopharmaceutical has been obtained with a concentration of 40-50 mg of glucoheptonic acid-calcium salt and not less than 0.45 mg of SnCl2 2 H2O at an optimal pH between 6.5 and 7.0. The stability of the complex has been found significantly affected when sodium hydroxide solution was used for the pH adjustment. However, an alternative procedure for final pH adjustment of the preparation has been investigated providing a stable complex for the usual period of time prior to the injection. The organ distribution and the blood clearance data of 99mTc-GH in rabbits were relatively similar to those reported earlier. The mean concentration of the radiopharmaceutical in both kidneys has been studied in normal subjects for one hour with a scintillation camera and the results were satisfactory.

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