New approaches to the design of analgesic medicinal substances

2021 ◽  
Author(s):  
Ilya V. Rogachevskii ◽  
Vera B. Plakhova ◽  
Valentina A. Penniyaynen ◽  
Stanislav G. Terekhin ◽  
Svetlana A. Podzorova ◽  
...  
Keyword(s):  
Functional Groups ◽  
Receptor Binding ◽  
Therapeutic Potential ◽  
Medicinal Substance ◽  
Neuron Membrane ◽  
Comenic Acid ◽  
Structural Criterion ◽  
Calcium Cations ◽  
Medicinal Substances ◽  
Living Neurons

A gamma-pyrone derivative, comenic acid, activates the opioid-like receptor-mediated signaling pathway that modulates the NaV1.8 channels in the primary sensory neuron membrane. These channels are responsible for generation of the nociceptive signal; gamma-pyrones can therefore have a great therapeutic potential as analgesics, and this effect deserves a deeper understanding. The novelty of our approach to the design of a medicinal substance is based on a combination of the data obtained on living neurons using very sensitive physiological methods and the results of quantum-chemical calculations. This approach allows to correlate the molecular structure of gamma-pyrones with their ability to evoke a physiological response of the neuron. Comenic acid can bind two calcium cations. One of them is chelated by the carbonyl and the hydroxyl functional groups, while another one forms the salt bond with the carboxylate anion. Calcium-bound gamma-pyrones are fundamentally different in electrostatic properties from the free gamma-pyrone molecules. These two calcium ions are the key elements involved in ligand-receptor binding. It is very likely ion-ionic interactions between these cations and anionic functional groups of the opioid-like receptor that activate the latter. The calculated intercationic distance of 9.5 Å is a structural criterion for effective ligand-receptor binding of calcium-bound gamma-pyrones.

scholarly journals The Role of Phytodiversity in Riparian Alder Forests in Supporting the Provision of Ecosystem Services

2016 ◽  
Vol 13 (2) ◽  
pp. 47-51
Author(s):  
Patrícia Mariničová ◽  
Pavol Eliáš
Keyword(s):  
Ecosystem Services ◽  
Species Diversity ◽  
Medicinal Plants ◽  
Functional Groups ◽  
Functional Diversity ◽  
Woody Plants ◽  
Forest Ecosystems ◽  
Therapeutic Potential ◽  
Human Society

Abstract Nature, ecosystems and biodiversity provide human society with many benefits known as ecosystem services. Functional diversity is an important aspect of biodiversity. In this paper, we applied inductive approach to the identification, mapping and evaluation of ecosystem services of the Aegopodio-Alnetum glutinosae community in Tribeč Mts. The results from 2015 show that the alder floodplain forest represents one of the most productive forest ecosystems with seasonal maximum production of 59.03 g m−2, species diversity of N0 = 40 and functional diversity of FD = 10. The forage potential of this community is medium, the melliferous potential is high and the therapeutic potential was estimated as extremely rich in medicinal plants. From the functional groups for providing ecosystem services, woody plants and hemicryptophytes play the most significant role.

scholarly journals Pembuatan Protokol Penapisan Virtual Berbasis Stuktur (pvbs) untuk Identifikasi Ligan Inhibitor Reseptor Platelet-Activating Factor (PAF-r) sebagai Target Terapeutik Asma menggunakan YASARA

2020 ◽  
Vol 11 (1) ◽  
pp. 35-42
Author(s):  
Gerry Nugraha ◽  
Enade Perdana Istyastono
Keyword(s):  
Crystal Structure ◽  
Receptor Binding ◽  
Therapeutic Potential ◽  
Platelet Activating Factor ◽  
Data Bank ◽  
Time Interval ◽  
Internal Validation ◽  
Asthma Patients ◽  
Screening Protocol ◽  
Dynamics Simulations

Platelet-activating factor receptors (PAF-r) is known as one of the receptors that affect asthma, while the Y-21480 ligand is reported as an effective, specific, and active PAF-r antagonist for asthma patients. Research in building structure-based virtual screening protocol (SBVS) for identification of PAF-r ligand inhibitors has been performed, the receptor crystal structure was obtained from the Protein Data Bank (PDB ID: 5zkp), while the ligand used as a leading compound is Y-24180, obtained from U.S. National Library of Medicine. Interactions between ligands and receptors are observed through molecular dynamics simulations using the YASARA program at intervals up to 20 nanoseconds, ligand-receptor binding stability occurs after a time interval of 2 nanoseconds, the lowest ligand-receptor binding energy occurs at a time interval of 1,401 picoseconds. Internal validation by re-docking 1,000 times the ligand to receptor resulted in a value of Root Mean Square Deviation (RMSD) of 0.6037 Å,  confirmed that SBVS protocol was accurately able to reproduce the Y-24180 ligand pose on the 5zkp crystal structure,  the protocol can be used as a new approach for investigation or design of compounds that have therapeutic potential as anti-asthma.

Distributor for bronchoscope suction

1982 ◽  
Vol 63 (1) ◽  
pp. 64-65
Author(s):  
G. I. Kirshin ◽  
A. M. Korepanov
Keyword(s):  
Medicinal Substance ◽  
Medicinal Substances ◽  
Two Stages

An integral part of bronchoscopy, widely used in pulmonology, is the suction of the contents of the bronchi and the introduction of medicinal substances. The procedure is carried out in two stages: first, the contents of the bronchi are removed by suction of the bronchoscope into the aspiration pump, which is then disconnected, and then a solution of the medicinal substance is injected through the suction of the bronchoscope or a special tube. Subsequently, these operations are repeated. Such disconnected procedures make bronchial sanitation laborious and time-consuming, which leads to hypoxia and hypercapnia of the patient, the loss of a part of the medicinal substance.

scholarly journals Deconstructing Mitochondrial Dysfunction in Alzheimer Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Vega García-Escudero ◽  
Patricia Martín-Maestro ◽  
George Perry ◽  
Jesús Avila
Keyword(s):  
Alzheimer Disease ◽  
Mitochondrial Dysfunction ◽  
Therapeutic Potential ◽  
Dynamic Balance ◽  
Mitochondrial Damage ◽  
Mitochondrial Dynamic ◽  
Cellular Models ◽  
Mitochondrial Alterations ◽  
Direct Transdifferentiation ◽  
Living Neurons

There is mounting evidence showing that mitochondrial damage plays an important role in Alzheimer disease. Increased oxygen species generation and deficient mitochondrial dynamic balance have been suggested to be the reason as well as the consequence of Alzheimer-related pathology. Mitochondrial damage has been related to amyloid-beta or tau pathology or to the presence of specific presenilin-1 mutations. The contribution of these factors to mitochondrial dysfunction is reviewed in this paper. Due to the relevance of mitochondrial alterations in Alzheimer disease, recent works have suggested the therapeutic potential of mitochondrial-targeted antioxidant. On the other hand, autophagy has been demonstrated to play a fundamental role in Alzheimer-related protein stress, and increasing data shows that this pathway is altered in the disease. Moreover, mitochondrial alterations have been related to an insufficient clearance of dysfunctional mitochondria by autophagy. Consequently, different approaches for the removal of damaged mitochondria or to decrease the related oxidative stress in Alzheimer disease have been described. To understand the role of mitochondrial function in Alzheimer disease it is necessary to generate human cellular models which involve living neurons. We have summarized the novel protocols for the generation of neurons by reprogramming or direct transdifferentiation, which offer useful tools to achieve this result.

Comenic acid decreases the impulse frequency of the nociceptive neuron membrane

2015 ◽  
Vol 462 (1) ◽  
pp. 155-157 ◽  
Author(s):  
O. E. Dick ◽  
T. N. Shelykh ◽  
V. B. Plakhova ◽  
A. D. Nozdrachev ◽  
B. V. Krylov
Keyword(s):  
Nociceptive Neuron ◽  
Impulse Frequency ◽  
Neuron Membrane ◽  
Comenic Acid

scholarly journals Structural Basis of SARS-CoV-2– and SARS-CoV–Receptor Binding and Small-Molecule Blockers as Potential Therapeutics

2021 ◽  
Vol 61 (1) ◽  
pp. 465-493 ◽  
Author(s):  
Hariharan Sivaraman ◽  
Shi Yin Er ◽  
Yeu Khai Choong ◽  
Edem Gavor ◽  
J. Sivaraman
Keyword(s):  
Small Molecule ◽  
Receptor Binding ◽  
Viral Entry ◽  
Small Molecule Inhibitors ◽  
Therapeutic Potential ◽  
Structural Basis ◽  
Virus Receptor ◽  
Fusion Inhibitors ◽  
Human Coronaviruses ◽  
Transmembrane Serine Protease

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other hosts is mediated by host–pathogen interactions, specifically virus–receptor binding. An in-depth understanding of the virus–receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus–receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RNA-dependent RNA polymerase, against human coronaviruses, including SARS-CoV-2.

A Novel Somatostatin Mimic with Broad Somatotropin Release Inhibitory Factor Receptor Binding and Superior Therapeutic Potential

2003 ◽  
Vol 46 (12) ◽  
pp. 2334-2344 ◽  
Author(s):  
Ian Lewis ◽  
Wilfried Bauer ◽  
Rainer Albert ◽  
Nagarajan Chandramouli ◽  
Janos Pless ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Therapeutic Potential ◽  
Inhibitory Factor

scholarly journals Preparation and Characterization of Indomethacin Supramolecular Systems with β-Cyclodextrin in Order to Estimate Photostability Improvement

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7436
Author(s):  
Marzena Jamrógiewicz ◽  
Marek Józefowicz
Keyword(s):  
Inclusion Complexes ◽  
Therapeutic Potential ◽  
Solid Phase ◽  
Supramolecular Complexes ◽  
Supramolecular Systems ◽  
Medicinal Substances ◽  
Photochemical Stability ◽  
Dsc Calorimetry ◽  
Physical Mixtures

Cyclodextrins have found wide application in contemporary chemistry, pharmacy and medicine. Because of their unique properties, cyclodextrins are constantly used in research on solubility or stability improvement, as well as other physicochemical properties of medicinal substances. Indomethacin (IND) is a photolabile molecule that also attracts the interest of researchers due to its therapeutic potential and the need to overcome its problematic photosensitivity. Supramolecular complexes of indomethacin with β-cyclodextrin (CD) are already known, and they show greater stability compared to complexes with other types of cyclodextrins. So far, however, the sensitivity to light of physical mixtures and inclusion complexes in the solid phase has not been studied, and their various stoichiometries have not yet been investigated. Due to this fact, the aim of the present study is to obtain supramolecular systems (inclusion complexes and physical mixtures) of indomethacin with three different amounts of β-cyclodextrin. Assessment of the photochemical stability of indomethacin-β-cyclodextrin systems in the solid state is performed in order to find the best correlation between IND stability and the amount of CD. Comparative analysis of physicochemical degradation for stoichiometry systems [CD:IND] = [1:1], [0.5:1] and [0.1:1] is performed by using ultraviolet spectroscopy, transmission—FTIR, reflection—ATR-FTIR infrared spectroscopy and DSC calorimetry.

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