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E. ALPER TURKOGLU ET AL.
76
inhibitor in this series of derivatives were compound 11 with a KI 10. Le Darz A, Mingot A, Bouazza F, et al. Fluorinated pyrroli-
dines and piperidines incorporating tertiary benzenesulfona-
mide moieties are selective carbonic anhydrase II inhibitors.
J Enzyme Inhib Med Chem 2015;30:737–45.
of 0.1715 mM.
In a recent study it was reported that catechol and resorcinol27
act as a CAI inhibitor, and could represent the starting point for a
new class of inhibitors that may have advantages for patients with
sulfonamide allergies. The sulfonamide zinc-binding group is thus
superior to the thiol one (from the thioxolone hydrolysis product)
for generating CA inhibitors with a varied and sometimes isozyme-
selective inhibition profile against the mammalian enzymes.
However, it is still important to explore further classes of potent
CAIs in order to detect compounds with different inhibition
profiles.
11. Masini E, Carta F, Scozzafava A, Supuran CT. Antiglaucoma
carbonic anhydrase inhibitors: a patent review. Expert Opin
Ther Patents 2013;23:705–16.
12. Orhan F, Senturk M, Supuran CT. Interaction of anions with
a
newly characterized alpha carbonic anhydrase from
Halomonas sp. J Enzyme Inhib Med Chem 2015. [Epub
13. Arslan T, Celik G, Celik H, et al. Synthesis and biological
evaluation of novel bischalcone derivatives as carbonic
anhydrase inhibitors. Arch Pharm (Weinheim) 2016;349:
741–8.
14. Karatas MO, Alici B, Cakir U, et al. Syhthesis and carbonic
anhydrase inhibitory properties of novel coumarin deriva-
tives. J Enzyme Inhib Med Chem 2013;28:299–304.
15. Yaseen R, Ekinci D, Senturk M, et al. Pyridazinone substituted
benzenesulfonamides as potent carbonic anhydrase inhibi-
tors. Bioorg Med Chem Lett 2016;26:1337–41.
Compounds 3–12 used in this study affect the activity of CA
isozymes due to the presence of the different functional groups
(CH3, OH, Br, COOH, NH2, mesityl, and tosyl) present in their scaf-
fold. Therefore, our findings indicate another class of possible CAIs
of interest, in addition to the well-known inhibitors, the phenols/
biphenyl diphenols bearing bulky ortho moieties in their mole-
cules. Some hyroxylic compounds investigated here exhibited
effective hCA I and II inhibitory activity, in the low-micromolar
range, by the esterase method which usually gives KI-s an order of
magnitude higher as compared to the CO2 hydrase assay. These
findings point out that substituted hdroxylic compounds may be
used as leads for generating potent CAIs eventually targeting
other isoforms.
16. Isık S, Vullo D, Durdagi S, et al. Interaction of carbonic anhy-
drase isozymes I, II, and IX with some pyridine and phenol
hydrazinecarbothioamide derivatives. Bioorg Med Chem Lett
2015;25:5636–41.
17. Guney M, Cavdar H, Senturk M, Ekinci D. Synthesis and car-
bonic anhydrase inhibitory properties of novel uracil deriva-
tives. Bioorg Med Chem Lett 2015;25:3261–3.
18. Ozdemir ZO, Senturk M, Ekinci D. Inhibition of mammalian
carbonic anhydrase isoforms I, II and VI with thiamine and
thiamine-like molecules. J Enzyme Inhib Med Chem 2013;28:
316–19.
Disclosure statement
The authors report no declarations of interest
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