Department of Chemistry, Arts and Science Faculty, Dumlupinar University, Kütahya, Turkey.
J Pharm Pharmacol. 2013 Mar;65(3):363-9. doi: 10.1111/j.2042-7158.2012.01609.x. Epub 2012 Nov 15.
Two new metal complexes, diaquabis(4-benzoyl-1,5-diphenyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3-carboxamide)cobalt(II) dihydrate (2) and diaquabis(ethyl-1-(3-nitrophenyl)-5-phenyl-3-(5-sulfamoyl-1,3,4-thiadiazol-2-ylcarbamoyl)-1H-pyrazole-4-carboxylate)cobalt(II) monohydrate (4), containing sulfonamide have been synthesized by the reaction of Co(II) with 4-benzoyl-1,5-diphenyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3-carboxamide (1) and ethyl-1-(3-nitrophenyl)-5-phenyl-3-(5-sulfamoyl-1,3,4-thiadiazol-2-ylcarbamoyl)-1H-pyrazole-4-carboxylate (3), respectively.
The structures of Co(II) complexes 2 and 4 have been characterised by spectroscopic methods and elemental analyses. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of ligands 3 and 4, acetazolamide as a control compound and the newly synthesized complexes on the activity of hydratase and esterase of these isoenzymes have been studied in vitro.
The concentration of compounds 2 and 4 producing a 50% inhibition of hydratase activity (IC(50) values) were 0.473 ± 0.025 and 0.065 ± 0.002 μm for hCA-I and 0.213 ± 0.015 and 0.833 ± 0.021 μm for hCA-II, respectively. The IC(50) values of synthesized compounds 2 and 4 for esterase activity were, 0.058 ± 0.006 and 0.297 ± 0.015 μm for hCA-I and 0.110 ± 0.010 and 0.052 ± 0.002 μm for hCA-II, respectively. In relation to esterase activity, the inhibition equilibrium constants (K(i) ) were determined as 0.039 ± 0.004 and 0.247 ± 0.035 μm on hCA-I and 0.078 ± 0.002 and 0.363 ± 0.015 μm on hCA-II for 2 and 4, respectively.
The synthesized compounds 2 and 4 had effective inhibitory activity (P < 0.0001) on hCA-I and hCA-II than the corresponding free ligands, 1 and 3, and acetazolamide. Compounds 2 and 4 might be considered as potential inhibitors.
通过 Co(II)与 4-苯甲酰基-1,5-二苯基-N-(5-磺酰胺基-1,3,4-噻二唑-2-基)-1H-吡唑-3-羧酰胺（1）和乙基-1-(3-硝基苯基）-5-苯基-3-(5-磺酰胺基-1,3,4-噻二唑-2-基甲酰胺基)-1H-吡唑-4-羧酸盐（3）的反应，合成了两种新的金属配合物，二水合二（4-苯甲酰基-1,5-二苯基-N-(5-磺酰胺基-1,3,4-噻二唑-2-基)-1H-吡唑-3-羧酰胺）钴(II)（2）和一水合二（乙基-1-(3-硝基苯基）-5-苯基-3-(5-磺酰胺基-1,3,4-噻二唑-2-基甲酰胺基)-1H-吡唑-4-羧酸盐）钴(II)（4），它们都含有磺酰胺。
通过光谱方法和元素分析对 Co(II)配合物 2 和 4 的结构进行了表征。人碳酸酐酶同工酶（hCA-I 和 hCA-II）通过亲和层析从红细胞中纯化得到。研究了配体 3 和 4、对照化合物乙酰唑胺以及新合成的配合物对这些同工酶水合酶和酯酶活性的抑制作用。
化合物 2 和 4 抑制 hCA-I 水合酶活性的半抑制浓度（IC50 值）分别为 0.473 ± 0.025 和 0.065 ± 0.002 μm，对 hCA-II 的 IC50 值分别为 0.213 ± 0.015 和 0.833 ± 0.021 μm。合成化合物 2 和 4 对 hCA-I 酯酶活性的 IC50 值分别为 0.058 ± 0.006 和 0.297 ± 0.015 μm，对 hCA-II 的 IC50 值分别为 0.110 ± 0.010 和 0.052 ± 0.002 μm。关于酯酶活性，对 hCA-I 和 hCA-II 的抑制平衡常数（K(i)）分别为 0.039 ± 0.004 和 0.247 ± 0.035 μm和 0.078 ± 0.002 和 0.363 ± 0.015 μm。
与相应的游离配体 1 和 3 以及乙酰唑胺相比，合成的化合物 2 和 4 对 hCA-I 和 hCA-II 具有有效的抑制活性（P<0.0001）。化合物 2 和 4 可能被认为是潜在的抑制剂。
