Synthesis and biological evaluation of a new series of ebselen derivatives as glutathione peroxidase (GPx) mimics and cholinesterase inhibitors against Alzheimer's disease.

Bioorg Med Chem

Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address:

Published: February 2014

A series of ebselen derivatives were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and glutathione peroxidase (GPx) mimics. Most of the compounds were found to be potent against AChEs and BuChE, compounds 5e and 5i, proved to be the most potent against AChE with IC₅₀ values of 0.76 and 0.46 μM, respectively. Among these hybrids, most of the compounds were found to be good GPx mimics compare with ebselen. The selected compounds 5e and 5i were also used to determine the catalytic parameters and in vitro hydrogen peroxide scavenging activity. The results indicate that compounds 5e and 5i may be excellent multifunctional agents for the treatment of AD.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2013.12.066DOI Listing

Publication Analysis

Top Keywords

gpx mimics
12
series ebselen
8
ebselen derivatives
8
glutathione peroxidase
8
peroxidase gpx
8
compounds
5
synthesis biological
4
biological evaluation
4
evaluation series
4
derivatives glutathione
4

Similar Publications

Multienzyme-mimic Fe single-atom nanozymes regulate infection microenvironment for photothermal-enhanced catalytic antibacterial therapy.

Colloids Surf B Biointerfaces

January 2025

Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital & Center for Molecular Imaging Probe & Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address:

The rational design of nanozymes with highly efficient reactive oxygen species (ROS) generation to overcome the resistant infection microenvironment still faces a significant challenge. Herein, the highly active Fe single-atom nanozymes (Fe SAzymes) with a hierarchically porous nanostructure were prepared through a colloidal silica-induced template method. The proposed Fe SAzymes with satisfactory oxidase (OD)-like and peroxidase (POD)-like activity can transform O and HO to superoxide anion free radical (•O) and hydroxyl radical (•OH), which possess an excellent bactericidal effect.

View Article and Find Full Text PDF

A prospective therapeutic strategy: GPX4-targeted ferroptosis mediators.

Eur J Med Chem

January 2025

Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, PR China. Electronic address:

As a crucial regulator of oxidative homeostasis, seleno-protein glutathione peroxidase 4 (GPX4) represents the primary defense system against ferroptosis, making it a promising target with important clinical application prospects. From the discovery of covalent and allosteric sites in GPX4, substantial advancements in GPX4-targeted small molecules have been made through diverse discovery and design strategies in recent years. Moreover, as an emerging hotspot in drug development, seleno-organic compounds can functionally mimic GPX4 to reduce hydroperoxides.

View Article and Find Full Text PDF

Background: Physiologically relevant cell line-based models of human airway mucosa are needed to assess nanoparticle-mediated pulmonary toxicity for any xenbiotics expsoure study. Palladium nanoparticles (Pd-NP) originating from catalytic converters in vehicles pose health risks. We aimed to develop airway models to assess the toxic potential of Pd-NP in normal (Non-CB) and chronic bronchitis-like (CB-like) mucosa models.

View Article and Find Full Text PDF
Article Synopsis
  • Nonmetal-containing peroxidase enzymes, such as glutathione peroxidase, help maintain cellular redox levels by reducing hydrogen peroxide through a dual-attack mechanism.
  • Researchers synthesized two compounds that mimic this GPx-like activity by incorporating a selenolate group and a proton donor, significantly enhancing their ability to cleave the O-O bond in hydrogen peroxide.
  • These compounds not only exhibit strong antioxidant properties but also protect metal complexes from oxidative stress by acting as sacrificial antioxidants, thus preventing the production of reactive oxygen species (ROS).
View Article and Find Full Text PDF

Determination of the role of miR-451a on Plasmodium falciparum red blood cell stages, oxidative stress, and proteomic profiling.

Mol Biol Rep

October 2024

Department of Zoology, BMTC, Human Genetics and WLC, School of Sciences, Gujarat University, Ahmedabad, Gujarat, 380009, India.

Background: This study examines the feasibility and effects of introducing microRNA mimic into red blood cells (RBCs) at the initial phases of Plasmodium falciparum 3D7 (Pf3D7) infection. The aim is to determine the correlation between increased expression of miR-451a and parasitaemia.

Methods: In this study miR-mimic-451a labelled with Cy3 and transfected into control and infected RBCs using lipofectamine and analysed using the fluorescence microscopy and flow cytometry.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!