scholarly journals Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Anders Bach ◽  
Søren W. Pedersen ◽  
Liam A. Dorr ◽  
Gary Vallon ◽  
Isabelle Ripoche ◽  
...  
Keyword(s):  
Small Molecules ◽  
Mechanism Of Action ◽  
Potential Inhibitors

scholarly journals Techniques to Study Inflammasome Activation and Inhibition by Small Molecules

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1704
Author(s):  
Diego Angosto-Bazarra ◽  
Cristina Molina-López ◽  
Alejandro Peñín-Franch ◽  
Laura Hurtado-Navarro ◽  
Pablo Pelegrín
Keyword(s):  
Inflammatory Response ◽  
Small Molecules ◽  
Mechanism Of Action ◽  
Inflammatory Diseases ◽  
Inflammasome Activation ◽  
Chronic Inflammatory Diseases ◽  
Anti Inflammatory ◽  
Inhibitory Molecules ◽  
Inflammasome Inhibitors

Inflammasomes are immune cytosolic oligomers involved in the initiation and progression of multiple pathologies and diseases. The tight regulation of these immune sensors is necessary to control an optimal inflammatory response and recover organism homeostasis. Prolonged activation of inflammasomes result in the development of chronic inflammatory diseases, and the use of small drug-like inhibitory molecules are emerging as promising anti-inflammatory therapies. Different aspects have to be taken in consideration when designing inflammasome inhibitors. This review summarizes the different techniques that can be used to study the mechanism of action of potential inflammasome inhibitory molecules.

scholarly journals Ru(II)-Dppz Derivatives and Their Interactions with DNA: Thirty Years and Counting

2021 ◽  
Vol 11 (7) ◽  
pp. 3038
Author(s):  
Maria Letizia Di Pietro ◽  
Giuseppina La Ganga ◽  
Francesco Nastasi ◽  
Fausto Puntoriero
Keyword(s):  
Transition Metal ◽  
Metal Complexes ◽  
Small Molecules ◽  
Transition Metal Complexes ◽  
Mechanism Of Action ◽  
Spectroscopic Techniques ◽  
Biological Applications ◽  
Ancillary Ligands ◽  
Structural Modifications ◽  
Over Time

Transition metal complexes with dppz-type ligands (dppz = dipyrido[3,2-a:2′,3′-c]phenazine) are extensively studied and attract a considerable amount of attention, becoming, from the very beginning and increasingly over time, a powerful tool for investigating the structure of the DNA helix. In particular, [Ru(bpy)2(dppz)]2+ and [Ru(phen)2(dppz)]2+ and their derivatives were extensively investigated as DNA light-switches. The purpose of this mini-review, which is not and could not be exhaustive, was to first introduce DNA and its importance at a biological level and research in the field of small molecules that are capable of interacting with it, in all its forms. A brief overview is given of the results obtained on the Ru-dppz complexes that bind to DNA. The mechanism of the light-switch active in this type of species is also briefly introduced along with its effects on structural modifications on both the dppz ligand and the ancillary ligands. Finally, a brief mention is made of biological applications and the developments obtained due to new spectroscopic techniques, both for understanding the mechanism of action and for cellular imaging applications.

scholarly journals Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules

2020 ◽  
Vol 14 ◽  
pp. 117793222096550
Author(s):  
Loubna Allam ◽  
Fatima Ghrifi ◽  
Hakmi Mohammed ◽  
Naima El Hafidi ◽  
Rachid El Jaoudi ◽  
...  
Keyword(s):  
Small Molecules ◽  
Binding Sites ◽  
Epigallocatechin Gallate ◽  
Host Cells ◽  
Spike Protein ◽  
Target Cells ◽  
Binding Affinities ◽  
Rapid Spread ◽  
Inhibitor Compounds ◽  
Potential Inhibitors

The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies. To this end, we aimed to explore novel inhibitor compounds that can stop replication or decrease the viral load of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is currently no approved treatment. Besides using the angiotensin-converting enzyme (ACE2) receptor as a main gate, the CoV-2 can bind to the glucose-regulating protein 78 (GRP78) receptor to get into the cells to start an infection. Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. These inhibitors were discovered through an approach of in silico screening of available databases of bioactive peptides and polyphenolic compounds and the analysis of their docking modes. This process led to the selection of 9 compounds with optimal binding affinities to the target sites. The peptides (satpdb18674, satpdb18446, satpdb12488, satpdb14438, and satpdb28899) act on regions III and IV of the viral Spike protein and on its binding sites in GRP78. However, 4 polyphenols such as epigallocatechin gallate (EGCG), homoeriodictyol, isorhamnetin, and curcumin interact, in addition to the Spike protein and its binding sites in GRP78, with the ATPase domain of GRP78. Our work demonstrates that there are at least 2 approaches to block the spread of SARS-CoV-2 by preventing its fusion with the host cells via GRP78.

scholarly journals Interactive Mechanism of Potential Inhibitors with Glycosyl for SARS-CoV-2 by Molecular Dynamics Simulation

Processes ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1749
Author(s):  
Yuqi Zhang ◽  
Li Chen ◽  
Xiaoyu Wang ◽  
Yanyan Zhu ◽  
Yongsheng Liu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Small Molecules ◽  
Binding Sites ◽  
Md Simulations ◽  
Experimental Methods ◽  
Dynamics Simulation ◽  
Theoretical Research ◽  
Stacking Interactions ◽  
Receptor Binding Domain ◽  
Potential Inhibitors

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a type of Ribonucleic Acid (RNA) coronavirus and it has infected and killed many people around the world. It is reported that the receptor binding domain of the spike protein (S_RBD) of the SARS-CoV-2 virus is responsible for attachment to human angiotensin converting enzyme II (ACE2). Many researchers are attempting to search potential inhibitors for fighting SARS-CoV-2 infection using theoretical or experimental methods. In terms of experimental and theoretical research, Cefuroxime, Erythromycin, Lincomycin and Ofloxacin are the potential inhibitors of SARS-CoV-2. However, the interactive mechanism of the protein SARS-CoV-2 and the inhibitors are still elusive. Here, we investigated the interactions between S_RBD and the inhibitors using molecular dynamics (MD) simulations. Interestingly, we found that there are two binding sites of S_RBD for the four small molecules. In addition, our analysis also illustrated that hydrophobic and π-π stacking interactions play crucial roles in the interactions between S_RBD and the small molecules. In our work, we also found that small molecules with glycosyl group have more effect on the conformation of S_RBD than other inhibitors, and they are also potential inhibitors for the genetic variants of SARS-CoV-2. This study provides in silico-derived mechanistic insights into the interactions of S_RBD and inhibitors, which may provide new clues for fighting SARS-CoV-2 infection.

BIOLOGIC AGENTS AND SMALL MOLECULES – MECHANISM OF ACTION

2022 ◽  
pp. 100861
Author(s):  
Katherine Falloon ◽  
Ruthvik Padival ◽  
Satya Kurada ◽  
Sara El Ouali ◽  
Florian Rieder
Keyword(s):  
Small Molecules ◽  
Mechanism Of Action ◽  
Biologic Agents
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