Synthesis and characterisation of two novel proton transfer compounds and their inhibition studies on carbonic anhydrase isoenzymes.
Two novel proton transfer compounds were prepared between 2,4-dichloro-5-sulphamoylbenzoic acid (lasamide) (Hsba) and ethylenediamine (en), namely ethane-1,2-diaminium 2,4-dichloro-5-sulphamoylbenzoate (1), and also between Hsba and 2-amino-3-methylpyridine (2-amino-3-picoline) (amp), namely 2-amino-3-methylpyridinium 2,4-dichloro-5-sulphamoylbenzoate (2). All these were characterised by elemental, spectral (IR and UV-vis), thermal analyses, and single crystal X-ray diffraction studies. Compounds 1 and 2 crystallised in the P-1 and P21/c space groups, respectively. Intermolecular non-covalent interactions, such as ion pairing, hydrogen bonding, and π-π stacking were observed for these ionic compounds. The free ligands Hsba, en and amp, the products 1 and 2, and acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibitor effects on the human carbonic anhydrase isoenzymes (hCA I and hCA II) purified from erythrocyte cells by affinity chromatography for their hydratase and esterase activities. The half maximal inhibitory concentration (IC(50)) values for products 1 and 2 with respect to hydratase activity are 0.15 and 0.32 μM for hCA I and 0.06 and 0.15 μM for hCA II, respectively. The IC(50) values of the same inhibitors for esterase activity are 0.13 and 0.8 μM for hCA I and 0.14 and 0.1 μM for hCA II, respectively. In relation to esterase activities, the inhibition equilibrium constants (Ki) were also determined and found to be 0.137 and 0.99 μM on hCA I and 0.157 and 0.075 μM on hCA II for 1 and 2, respectively. The comparison of the inhibition studies of the newly synthesised compounds 1 and 2 to the parent compounds Hsba and amp and also to AAZ indicated that 1 and 2 have an effective inhibitory activity on hCA I and II, and might be used as potential inhibitors.
Yenikaya
Cengiz
C
Department of Chemistry, Faculty of Arts and Sciences, Dumlupinar University, Kütahya, Turkey. yenikaya@dumlupinar.edu.tr
Sari
Musa
M
Bülbül
Metin
M
Ilkimen
Halil
H
Cinar
Burcu
B
Büyükgüngör
Orhan
O
D000086:Acetazolamide / Q000378:metabolism / Q000494:pharmacology; D000631:Aminopyridines / Q000737:chemistry; D000818:Animals; D001565:Benzoates / Q000737:chemistry; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D057075:Enzyme Assays; D004912:Erythrocytes / Q000201:enzymology; D005029:Ethylenediamines / Q000737:chemistry; D005901:Glaucoma / Q000517:prevention & control; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D010847:Picolines / Q000737:chemistry; D011522:Protons; D013057:Spectrum Analysis
D000631:Aminopyridines; D001565:Benzoates; D002257:Carbonic Anhydrase Inhibitors; D005029:Ethylenediamines; D007527:Isoenzymes; D010847:Picolines; D011522:Protons; C031234:ethylenediamine; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; C519313:2,4-dichloro-5-sulfamoylbenzoic acid; D000086:Acetazolamide; C109727:2-amino-3-methylpyridine