Received: 5 December 2017 Revised: 24 December 2017 Accepted: 27 December 2017
The determination of the carbonic anhydrases activators
in vitro effect of mixed donor crown ethers
Faculty of Engineering and Architecture, Food
Engineering, Siirt University, Siirt 56100, Turkey
Science and Technology Research and Applica-
tion Center, Siirt University, Siirt 56100, Turkey
Department of Chemistry, Faculty of Arts and
Sciences, Balikesir University, Balikesir 10145,
Vocational School of Health Services, Pharmacy
Services, Artvin Coruh University, Artvin 08000,
Carbonic anhydrases (CAs) play an important function in various physiological and pathological
processes. Therefore, many researchers work in this field in order to design and synthesize new
drugs. Both inhibitors and activators of CAs, which are associated with the diagnosis and treat-
ment of many diseases, are very important. The emergence of the use of CA activators in the
treatment of Alzheimer has led many scholars to work on this issue. In this study, CA activators
and inhibitors are determined. The crown ethers compounds (1, 2, 3, 6, 7, 8,and9) were found to
cause activation on enzyme activities of hCA I and II. The AC
values on hCA I and II of the com-
pounds are in the range of 4.6565–374.979 M. The 4 (IC
; 1.301 and 3.215 M for hCA I and II)
and 5 (IC
; 73.96 and 378.5 M for hCA I and II) compounds were found to cause inhibition on
enzyme activities of hCA I and II.
activation, carbonic anhydrase, inhibition, mixed donor crown ether
Alpha-carbonic anhydrases (CAs, EC22.214.171.124) of which minimum 16 dif-
ferent isoenzymes have been detected in mammalian tissue have very
critical physiologic roles.
These 16 isoenzymes are present in differ-
ent tissues and in different locations of the cell (i.e., cytosolic: CA I, II,
III, and VII; membrane associated: CA IV, IX, XII, XIV, and XV; mitochon-
drial: CA VA and VB; secreted in saliva: CA VI).
These enzymes are
very efficient catalysts for the reversiblehydration of carbon dioxide to
CAs are also known to catalyze many different hydra-
(for example: the hydration of cyanamide to urea, or
of cyanate to carbamic acid).
CA is a metalloenzyme with Zn
its active site. CAs are shown the wide distribution in many cells, tis-
sues, and organs.
CAs are contemplated as target enzymes to treat
or prevent a multitude of diseases as varied as diuretics,
gastric and duodenal ulcers,
among others, as well as antitumor
Furthermore, recent studies suggest that
CA activation may provide a novel therapy for Alzheimer's disease
When the association between CA enzyme and AD is analyzed, it
was seen that the enzyme decreased in the elderly and in patients
with AD. CA enzyme normally is seen to increase HCO
tion in memory-related nervous structures through a rapid and effec-
tive mechanism. Elevated HCO
flow changes neuronal responses
to various signal entries through synaptic GABA receptor channels.
CA function as an effective mechanism that controls signaling through
Synaptic spinal column changes and dendrite loss during
aging are known to lead to a significant reduction in cerebral CA and
this reduction is known to be more dramatic in brains of patients with
Phenyl-alanine, which is a CA I and II activator, was detected
to lead to a synaptic activity, spatial learning, and memorial phar-
macologic improvement when administered to test animals.
CA activators were not studied much until today. Histamine, sero-
tonin, catecholamines, dextrodopa,
-Adrenaline, and dopamine are some CA activators that have been
studied until today.
Novel inhibitors and activators of
the related enzyme are still being investigated by many scientists.
Therefore, crown ether derivatives that were not studied as activa-
tor/inhibitor before are investigated in the present study.
Crown ethers that were incidentally discovered by Charles Peder-
sen are multiple ring compounds that may be considered as polyethy-
lene glycol derivatives.
Oxocrown ethers have a good conforma-
tional flexibilitythrough their ring oligomeric structure. However, their
flexibility is restricted due to the likelihood of the presence of the
functional groups on it. These different structures of crown ethers
have enabled them to be able to be used in fields of supra-molecular
chemistry, analytic chemistry, biology, and most importantly phar-
macology besides the ability to interact with many different types
J Biochem Mol Toxicol. 2018;32:e22032.
2018 Wiley Periodicals, Inc. 1of5wileyonlinelibrary.com/journal/jbt