*Corresponding Author Address: Ludmila S. Bobkova, Department of the synthesis of biologically active substances, SI “Institute of
pharmacology and toxicology NAMS of Ukraine”, Kiev, Ukraine
World Journal of Pharmaceutical Sciences
ISSN (Print): 2321-3310; ISSN (Online): 2321-3086
Published by Atom and Cell Publishers © All Rights Reserved
Available online at: http://www.wjpsonline.org/
Original Article
Synthesis, antioxidant activity and QSAR studies of some pyridine derivatives
Ludmila S. Bobkova, Andrew R. Khairulin, Anatoly M. Demchenko, Tatiana A. Bukhtiarova
DОpartmОnt of tСО syntСОsis of bioloРiМally aМtivО substanМОs, SI “InstitutО of pСarmaМology and toxicology
NAMS of UkrainО”, KiОv, Ukraine
Received: 07-03-2015 / Revised: 25-03-2015 / Accepted: 09-04-2015
ABSTRACT
New quaternary pyridine salts and bases was synthesized and characterized in the presence of iminomethyl-
fragment containing the hydroxyl group or the hydroxy-ethyl group or the hydroxyphenyl group with imine
nitrogen atom. The synthesized compounds were tested in vitro for an antioxidant activity with a stable radical
2.2-diphenyl-1-picrylhydrazyl and reactivation ability of Sarin-inhibited AChE. The influence of antioxidant
activity parameters on reactivation ability and toxicity of the studied compounds was analyzed.
Key words: pyridine derivative, antioxidant activity, reactivation ability, QSAR studies
INTRODUCTION
The overproduction of cell free radicals affects
significantly on the development of many
pathological states. Protection against its excess
ensures the functioning of the cellular antioxidant
system [1]. The appearance of cancer,
arteriosclerosis, Alzheimer's disease is often
associated whit the action of free radicals [9].
The antioxidant activity of natural and synthetic
substances now is subject of very intensive studies
and considered as their important description. This
is evidenced by the large number of publications in
the scientific periodical literature. This is due, in
particular, with the fact that, as follows from the
literature data, it is antioxidant properties are
crucial in many aspects of the biological activity of
substances [5].
Reducing the toxicity of drugs can be achieved
through sharing with them the drugs of a class of
antioxidants, because oxidative stress is
accompanied by toxic effects of most xenobiotics
[7]. For example, one of the mechanisms of
toxicity of Adriamycin is a violation of pro - and
antioxidant balance and oxidative stress [15].
Antioxidants display a wide spectrum of
pharmacological activity and have anticancer, anti-
inflammatory, and regenerating properties [3, 4].
For example, the antioxidant activity of Dibunole
plays a role in the mechanism of its anti-cancer and
local anti-inflammatory action [16].
Found that many drugs with antioxidant properties
cause a pronounced anti-inflammatory effect. As a
probable mechanism of anti-inflammatory and
immunomodulatory effects may be assumed ability
of drugs to regulate the processes of free-radical
oxidation.
It is known that Uracil and its derivatives are
biologically active agents and are widely used in
medicine. One of the most important properties of
Uracil and its derivatives is their ability to slow
down the radical-chain process. To the present time
has been studied quite extensively reactivity of a
number of Uracil derivatives in the reactions of
chain breakage on peroxyl radicals [14].
By this time developed many different methods for
determination of antioxidant activity in vitro [11].
Methods for determination of antioxidant activity
of medicinal compounds using colored stable
radicals, based on the determination of the
reactivity of drugs by spectrophotometric method
or by the EPR method. Usually use stable free
radicals such as hydrazyl, nitroxyl, isolated in the
free state [13].
To study the activity of natural antioxidants is
commonly use the DPPH (2.2-diphenyl-1-
picrylhydrazyl) [4]. PubMed database shows that