scholarly journals Long-Lasting Effects of Oxy- and Sulfoanalogues of L-Arginine on Enzyme Actions

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Tatyana A. Dzimbova ◽  
Peter B. Milanov ◽  
Tamara I. Pajpanova
Keyword(s):  
Conformational Changes ◽  
Biological Effects ◽  
Docking Studies ◽  
Trna Synthetase ◽  
Physiological Conditions ◽  
Natural Processes ◽  
Arginine Mimetics ◽  
Arginine Residues ◽  
Structure Of Proteins ◽  
Cognate Trna

Arginine residues are very important for the structure of proteins and their action. Arginine is essential for many natural processes because it has unique ionizable group under physiological conditions. Numerous mimetics of arginine were synthesized and their biological effects were evaluated, but the mechanisms of actions are still unknown. The aim of this study is to see if oxy- and sulfoanalogues of arginine can be recognized by human arginyl-tRNA synthetase (HArgS)—an enzyme responsible for coupling of L-arginine with its cognate tRNA in a two-step catalytic reaction. We make use of modeling and docking studies of adenylate kinase (ADK) to reveal the effects produced by the incorporation of the arginine mimetics on the structure of ADK and its action. Three analogues of arginine, L-canavanine (Cav), L-norcanavanine (NCav), and L-sulfoarginine (sArg), can be recognized as substrates of HArgS when incorporated in different peptide and protein sequences instead of L-arginine. Mutation in the enzyme active center by arginine mimetics leads to conformational changes, which produce a decrease the rate of the enzyme catalyzed reaction and even a loss of enzymatic action. All these observations could explain the long-lasting nature of the effects of the arginine analogues.

Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors

2020 ◽  
Vol 75 (9-10) ◽  
pp. 353-362
Author(s):  
Begüm Nurpelin Sağlık ◽  
Ahmet Mücahit Şen ◽  
Asaf Evrim Evren ◽  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Biological Effects ◽  
Docking Studies ◽  
Benzimidazole Derivatives ◽  
Binding Modes ◽  
Reference Drug ◽  
In Silico Studies ◽  
New Compounds ◽  
Mcf 7

AbstractInhibition of aromatase enzymes is very important in the prevention of estrogen-related diseases and the regulation of estrogen levels. Aromatase enzyme is involved in the final stage of the biosynthesis of estrogen, in the conversion of androgens to estrogen. The development of new compounds for the inhibition of aromatase enzymes is an important area for medicinal chemists in this respect. In the present study, new benzimidazole derivatives have been designed and synthesized which have reported anticancer activity in the literature. Their anticancer activity was evaluated against human A549 and MCF-7 cell lines by MTT assay. In the series, concerning MCF-7 cell line, the most potent compounds were the 4-benzylpiperidine derivatives 2c, 2g, and 2k with IC50 values of 0.032 ± 0.001, 0.024 ± 0.001, and 0.035 ± 0.001 µM, respectively, compared to the reference drug cisplatin (IC50 = 0.021 ± 0.001 µM). Then, these compounds were subject to further in silico aromatase enzyme inhibition assays to determine the possible binding modes and interactions underlying their activity. Thanks to molecular docking studies, the effectiveness of these compounds against aromatase enzyme could be simulated. Consequently, it has been found that these compounds can be settled very properly to the active site of the aromatase enzyme.

scholarly journals Bioactivities of Centaurium erythraea (Gentianaceae) Decoctions: Antioxidant Activity, Enzyme Inhibition and Docking Studies

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3795 ◽  
Author(s):  
Laura Guedes ◽  
Pedro B. P. S. Reis ◽  
Miguel Machuqueiro ◽  
Asma Ressaissi ◽  
Rita Pacheco ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antioxidant Activities ◽  
Biological Effects ◽  
Radical Scavenging ◽  
Docking Studies ◽  
Top Down ◽  
Ache Inhibitors ◽  
Shape Complementarity ◽  
In Silico Molecular Docking ◽  
Centaurium Erythraea

Centaurium erythraea is recommended for the treatment of gastrointestinal disorders and to reduce hypercholesterolemia in ethno-medicinal practice. To perform a top-down study that could give some insight into the molecular basis of these bioactivities, decoctions from C. erythraea leaves were prepared and the compounds were identified by liquid chromatography-high resolution tandem mass spectrometry (LC–MS/MS). Secoiridoids glycosides, like gentiopicroside and sweroside, and several xanthones, such as di-hydroxy-dimethoxyxanthone, were identified. Following some of the bioactivities previously ascribed to C. erythraea, we have studied its antioxidant capacity and the ability to inhibit acetylcholinesterase (AChE) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Significant antioxidant activities were observed, following three assays: free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) reduction; lipoperoxidation; and NO radical scavenging capacity. The AChE and HMGR inhibitory activities for the decoction were also measured (56% at 500 μg/mL and 48% at 10 μg/mL, respectively). Molecular docking studies indicated that xanthones are better AChE inhibitors than gentiopicroside, while this compound exhibits a better shape complementarity with the HMGR active site than xanthones. To the extent of our knowledge, this is the first report on AChE and HMGR activities by C. erythraea decoctions, in a top-down analysis, complemented with in silico molecular docking, which aims to understand, at the molecular level, some of the biological effects ascribed to infusions from this plant.

scholarly journals Extracellular Vesicles Orchestrate Immune and Tumor Interaction Networks

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3696
Author(s):  
Kevin Ho Wai Yim ◽  
Ala’a Al Hrout ◽  
Simone Borgoni ◽  
Richard Chahwan
Keyword(s):  
Communication Networks ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Potential Role ◽  
Viral Infections ◽  
Biological Effects ◽  
Surface Markers ◽  
Physiological Conditions ◽  
Intercellular Communications

Extracellular vesicles (EVs) are emerging as potent and intricate intercellular communication networks. From their first discovery almost forty years ago, several studies have bolstered our understanding of these nano-vesicular structures. EV subpopulations are now characterized by differences in size, surface markers, cargo, and biological effects. Studies have highlighted the importance of EVs in biology and intercellular communication, particularly during immune and tumor interactions. These responses can be equally mediated at the proteomic and epigenomic levels through surface markers or nucleic acid cargo signaling, respectively. Following the exponential growth of EV studies in recent years, we herein synthesize new aspects of the emerging immune–tumor EV-based intercellular communications. We also discuss the potential role of EVs in fundamental immunological processes under physiological conditions, viral infections, and tumorigenic conditions. Finally, we provide insights on the future prospects of immune–tumor EVs and suggest potential avenues for the use of EVs in diagnostics and therapeutics.

scholarly journals A Study of QSAR based on Polynomial Modeling in Matlab

2019 ◽  
Vol 15 (15) ◽  
pp. 39 ◽  
Author(s):  
Fatima Sapundzhi ◽  
Tatyana Dzimbova
Keyword(s):  
Least Squares Method ◽  
Biological Effects ◽  
3D Structure ◽  
Docking Studies ◽  
In Vitro Tests ◽  
Biological Macromolecules ◽  
Polynomial Modeling ◽  
Relationship Of ◽  
The Relationship

Mu-opioid receptor (MOR) is an attractive target for <em>in silico</em> docking experiments. Many potent analgesics currently in use act through the MOR. The main objective of the present work was to find the polynomial function for modelling of the structure-activity relationship of a series of MOR analogues and the results of the molecular docking with MOR (PDBid:4dkl). The relationship of the biological activity of the ligands with the ChemScore function and with the total energy (MolDock function) was modelled with first- to third-degree polynomials and surface fitted method, assessed by least squares method. The finding, established in the paper, suggests that the third order polynomial could be successfully used for modelling of the relationship between the biological effect of the MOR analogues and results from docking procedure. Analysis and comparison of the data from in vitro tests and docking studies could help to understand better the relationship between in vitro biological effects and docking studies and to answer whether the models of the biological macromolecules (in our case MOR) correspond to the real 3D structure.

CORNEAL TOXICITY ASSOCIATED WITH AMMONIA EXPOSURE INVESTIGATED BY FOURIER TRANSFORM INFRARED SPECTROSCOPY

2009 ◽  
Vol 04 (04) ◽  
pp. 331-343 ◽  
Author(s):  
SHERIF SIDDICK MAHMOUD
Keyword(s):  
Fourier Transform ◽  
Infrared Spectroscopy ◽  
Fourier Transform Infrared Spectroscopy ◽  
Conformational Changes ◽  
Biological Effects ◽  
Exothermic Reaction ◽  
Fourier Transform Infrared ◽  
Gaseous Ammonia ◽  
Tissue Water ◽  
Ammonia Exposure

Chemical injury to the eye is still an important cause of blindness and serious complications. Gaseous ammonia combines with tissue water to form ammonium hydroxide ( NH 4 OH ). This exothermic reaction results in both heat and chemical burns. Although, over the years, the different biological effects of anhydrous ammonia are well known, its ocular effects are less clearly documented. This study reports the corneal structural alterations that may be induced as a result of ammonia exposure (gas or liquid) that was studied by Fourier transform infrared spectroscopy. The resulted IR spectra were analyzed using the band enhancement procedure. The obtained data clearly indicate that there are different structural and conformational changes (includes lipids and proteins) as the method of exposure to the ammonia differ, and due to the increased ammonia occupational exposure, there is an insistent need for the development of ophthalmic medications.

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