Glial adenosine kinase - A neuropathological marker of the epileptic brain
NEUROCHEMISTRY INTERNATIONAL
Authors: Aronica, Eleonora; Sandau, Ursula S.; Iyer, Anand; Boison, Detlev
Abstract
Experimental research over the past decade has supported the critical role of astrocytes activated by different types of injury and the pathophysiological processes that underlie the development of epilepsy. In both experimental and human epileptic tissues astrocytes undergo complex changes in their physiological properties, which can alter glio-neuronal communication, contributing to seizure precipitation and recurrence. In this context, understanding which of the molecular mechanisms are crucially involved in the regulation of glio-neuronal interactions under pathological conditions associated with seizure development is important to get more insight into the role of astrocytes in epilepsy. This article reviews current knowledge regarding the role of glial adenosine kinase as a neuropathological marker of the epileptic brain. Both experimental findings in clinically relevant models, as well as observations in drug-resistant human epilepsies will be discussed, highlighting the link between astrogliosis, dysfunction of adenosine homeostasis and seizure generation and therefore suggesting new strategies for targeting astrocyte-mediated epileptogenesis. (C) 2013 Elsevier Ltd. All rights reserved.
7-O-Arylmethylgalangin as a novel scaffold for anti-HCV agents
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Authors: Lee, Hyo Seon; Park, Kwang-su; Lee, Chaewoon; Lee, Bokhui; Kim, Dong-Eun; Chong, Youhoon
Abstract
In spite of potent antiviral activity, suboptimal physicochemical properties of aryl diketo acids (ADKs) necessitates modification of the core 1,3-diketo acid functionality into a novel scaffold. As the metal-binding affinity of the diketo acid is the key to the antiviral activity of ADKs, we anticipated 3,5-dihydroxy-4-oxo arrangement of galangin scaffold would serve as an excellent mimic for the diketo acid functionality. In this study, through synthesis and biological evaluation of various galangin derivatives, we have shown that the diketo acid functionality can be successfully replaced with the galangin scaffold by specific combination of the substituents to result in identification of a novel galangin derivative (3s) with anti-HCV activity (EC50 = 0.9 mu M) comparable to the ADK counterpart. (C) 2010 Elsevier Ltd. All rights reserved.