Design, synthesis and antiproliferative activity of new amine, amino acid and dipeptide-coupled benzamides as potential sigma-1 receptor

2020 ◽  
Vol 17 (10) ◽  
pp. 2515-2532 ◽  
Author(s):  
Eman Youssef ◽  
Mohamed Abd El-Moneim ◽  
Walid Fathalla ◽  
Mohamed S. Nafie
Keyword(s):  
Amino Acid ◽  
Antiproliferative Activity ◽  
Design Synthesis ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals Sigma-1 Receptor (S1R) Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases

2021 ◽  
Vol 22 (8) ◽  
pp. 4082
Author(s):  
Vladimir Zhemkov ◽  
Michal Geva ◽  
Michael R. Hayden ◽  
Ilya Bezprozvanny
Keyword(s):  
Endoplasmic Reticulum ◽  
Amino Acid ◽  
Ion Channels ◽  
Effector Proteins ◽  
Trophic Factors ◽  
Signaling Proteins ◽  
Sigma 1 Receptor ◽  
Experimental Systems ◽  
Sigma 1 ◽  
Signaling Receptors

The sigma-1 receptor (S1R) is a 223 amino acid-long transmembrane endoplasmic reticulum (ER) protein. The S1R modulates the activity of multiple effector proteins, but its signaling functions are poorly understood. S1R is associated with cholesterol, and in our recent studies we demonstrated that S1R association with cholesterol induces the formation of S1R clusters. We propose that these S1R-cholesterol interactions enable the formation of cholesterol-enriched microdomains in the ER membrane. We hypothesize that a number of secreted and signaling proteins are recruited and retained in these microdomains. This hypothesis is consistent with the results of an unbiased screen for S1R-interacting partners, which we performed using the engineered ascorbate peroxidase 2 (APEX2) technology. We further propose that S1R agonists enable the disassembly of these cholesterol-enriched microdomains and the release of accumulated proteins such as ion channels, signaling receptors, and trophic factors from the ER. This hypothesis may explain the pleotropic signaling functions of the S1R, consistent with previously observed effects of S1R agonists in various experimental systems.

scholarly journals Design, Synthesis, and Antidepressant Activity Study of Novel Aryl Piperazines Targeting Both 5-HT1A and Sigma-1 Receptors

2021 ◽  
Author(s):  
Yan-Na Ni ◽  
Xin-Li Du ◽  
Tao Wang ◽  
Yuan-Yuan Chen ◽  
Xiang-Qing Xu ◽  
...  
Keyword(s):  
Liver Microsomes ◽  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Metabolic Stability ◽  
Test Mouse ◽  
Design Synthesis ◽  
Sigma 1 Receptor ◽  
Piperazine Derivatives ◽  
Sigma 1

A total of 20 novel aryl piperazine derivatives were designed and synthesized, and their structures were confirmed by mass spectrometry and nuclear magnetic resonance analyses. Their 5-HT1A and sigma-1 receptor affinities were determined, and six of them showed high affinities (K i < 20 nmol/L) to both 5-HT1A and sigma-1 targets. Then, metabolic stability (T 1/2) tests of six compounds in rat and human liver microsomes were performed. Our data indicated that compound 27 has both high affinity for 5-HT1A and sigma-1 receptors (5-HT1A: K i = 0.44 nmol/L; sigma-1: K i = 0.27 nmol/L), and good metabolic stability (T 1/2 values are 21.7 and 24.6 minutes, respectively). Interestingly, results from the forced swimming test, mouse tail suspension test, and preliminary pharmacokinetic test suggested the marked antidepressant activity, good pharmacokinetic characteristics, and low toxicity of compound 27 in the two models. In conclusion, compound 27 has great value of further study as an active molecule of antidepressant drugs.

[123I]TPCNE: A novel SPET tracer for the sigma-1 receptor binds irreversibly in humans in vivo

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S655-S655
Author(s):  
James M Stone ◽  
Erik Arstad ◽  
Kjell Erlandsson ◽  
Rikki N Waterhouse ◽  
Peter J Ell ◽  
...  
Keyword(s):  
Sigma 1 Receptor ◽  
Sigma 1

Three Amino Acid Derivatives of Valproic Acid: Design, Synthesis, Theoretical and Experimental Evaluation as Anticancer Agents

2014 ◽  
Vol 14 (7) ◽  
pp. 984-993 ◽  
Author(s):  
Gabriela Luna-Palencia ◽  
Federico Martinez-Ramos ◽  
Ismael Vasquez-Moctezuma ◽  
Manuel Fragoso-Vazquez ◽  
Jessica Mendieta-Wejebe ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Amino Acid ◽  
Anticancer Agents ◽  
Experimental Evaluation ◽  
Amino Acid Derivatives ◽  
Design Synthesis ◽  
Derivatives Of

The Sigma-1 Receptor Ligands Chlorpromazine and Trifluoperazine Inhibit Na+ Transport in Frog Skin Epithelium

BIOPHYSICS ◽  
2020 ◽  
Vol 65 (5) ◽  
pp. 784-787
Author(s):  
A. V. Melnitskaya ◽  
Z. I. Krutetskaya ◽  
V. G. Antonov ◽  
N. I. Krutetskaya
Keyword(s):  
Frog Skin ◽  
Receptor Ligands ◽  
Na Transport ◽  
Sigma 1 Receptor ◽  
Skin Epithelium ◽  
Frog Skin Epithelium ◽  
Sigma 1

Design, Synthesis, and In Vitro Evaluation of Tubulin‐targeting Dibenzothiazines with Antiproliferative Activity as Novel Heterocycle Building Block

ChemMedChem ◽  
2021 ◽  
Author(s):  
Walter Damián Guerra ◽  
Daniel Lucena-Agell ◽  
Rafael Hortigüela ◽  
Roberto Arturo Rossi ◽  
J. Fernando Díaz ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Building Block ◽  
Design Synthesis ◽  
In Vitro Evaluation
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