The effect of vitamin C on carbonic anhydrase isoenzymes (hCA I and II)

Metabolik faaliyetlerin sorunsuz bir şekilde yerine getirilmesinde vitaminlerin önemi son derece büyüktür. Suda çözünen bir vitamin olan C vitamini, antioksidan özellik gösterir, nörotransmitasyonda ve kolajen sentezi gibi pek çok biyolojik süreçte rol alır. Karbonik anhidraz (CA) izoenzimleri ise elektrolit salınımı, pH dengesi, iyon taşınımı ve bunlarla ilişkili birçok süreçte rol alır. Çalışmamızda, C vitamininin, insan eritrositlerinden saflaştırılan hCA I ve hCA II üzerindeki inhibisyon etkileri in vitro olarak incelenmiştir. L-Askorbik asidin hCA I ve hCA II izoenzimlerini yarışmasız inhibisyon mekanizması üzerinden inhibe ettiği, Ki değerinin sırasıyla 96.8011.19 µM ve 120.4622.11 µM olduğu belirlenmiştir.Vitamins play an extremely important role in the smooth functioning of metabolic activities. Vitamin C, which is one of the water-soluble vitamins, has antioxidant properties and plays a role in many biological processes such as neurotransmission and collagen synthesis. Carbonic anhydrase (CA) enzymes play a role in electrolyte release, pH balance, ion transport and many related processes. In our study, the inhibition effects of vitamin C, on hCA I and hCA II purified from human erythrocytes were investigated as in vitro. It was determined that L-Ascorbic acid inhibits hCA I and hCA II isoenzymes through its non-competitive inhibition mechanism, and its Ki value was 96.8011.19 µM and 120.4622.11 µM, respectively

Carbonic anhydrase inhibitory activities of novel proton transfer salts and their Cu(II) complexes

In this study, two new proton transfer salts of sulfonamide derivatives of maleic acid, namely (ClHabt)+(mabsmal)– (1) and (ClHabt)+(pabsmal)– (2), were obtained from 2-amino-6-chlorobenzo­thiazole (Clabt) and N-(3-sulfamoylphenyl)maleamide acid (Hmabsmal) and N-(4-sulfamoyl­phenyl)maleamide acid (Hpabsmal), respectively. Also, the Cu(II) complexes (3 and 4) of salts (1 and 2) and of Hmabsmal (5) were prepared. Compounds 1‒5 were characterized by elemental, NMR (1H and 13C), FTIR, and thermal analyses, as well as UV-Vis, magnetic moment, and molar conductivity measurements. Carbonic anhydrase isoenzymes (hCA I and II) were purified from human erythrocyte cells by affinity chromatography. The effects of the synthesized compounds on the hydratase and esterase activities of CA isoenzymes were studied in vitro. The results reveal that the synthesized compounds inhibit both esterase and hydratase activities of hCA I and hCA II. The inhibition constants of the compounds (Ki) were determined according to the esterase activity measurements. Ki values of 1‒5 are in the range of 0.06 ± 0.003 µM and 4.25 ± 0.100 µM for hCA I, and of 0.02 ± 0.001 µM and 3.21 ± 0.200 µM for hCA II

2-Aminopiridin Türevleri ile Sülfonamit İçeren Maleamik Asit Türevinin Proton Transfer Tuzları ve Cu(II) Komplekslerinin Sentezi, Karakterizasyonu ve İnsan Eritrosit Karbonik Anhidraz İzoenzimleri Üzerindeki Etkilerinin İncelenmesi

Bu çalışmada, ilk olarak 3-aminobenzensülfonamit (mabs) ile maleik anhidritin (mal) tepkimesinden sülfonamit içeren maleamik asit türevi (E)-4-okso-4-(3-sülfamoyilfenil)amino)büt-2-enoik asit (Hmabsmal) bileşiği sentezlenmiştir. Daha sonra Hmabsmal bileşiği ile 2-aminopiridin türevlerinin [2-amino-3-metilpiridin (2a3mp) (1); 2-amino-4-metilpiridin (2a4mp) (2); 2-amino-5-metilpiridin (2a5mp) (3) veya 2-amino-6-metilpiridin (2a6mp) (4)] proton transfer tuzları hazırlanmıştır. 1 ve 3 tuzlarının Cu(II) (5 ve 6) geçiş metal kompleksleri sentezlenmiştir. Proton transfer tuzlarının yapısı elementel analiz, 1H-NMR, 13C-NMR, FT-IR, UV-Vis metotları ile aydınlatılmıştır. Amorf halde elde edilen geçiş metal komplekslerinin yapıları ise elementel analiz, ICP-OES, FT-IR, UV-Vis, termal analiz, manyetik duyarlılık ve molar iletkenlik sonuçları dikkate alınarak önerilmiştir. Ayrıca, sentezlenen maddelerin insan eritrosit hCA I ve hCA II izoenzimleri üzerindeki inhibisyon etkilerini belirlemek üzere in vitro çalışmalar yapılmıştır. Yeni sentezlenen maddelerin izoenzimlerin esteraz aktivitesini inhibe ettiği tespit edilmiştir. Özellikle 5 ve 6 bileşikleri kayda değer inhibisyon etkisine sahiptirler. Bu maddelerin inhibisyon değerlerinin kontrol bileşiği asetazolamit (AAZ) değerleri ile kıyaslanabilir büyüklükte olduğu tespit edilmiştir

Synthesis of novel sulfonamides under mild conditions with effective inhibitory activity against the carbonic anhydrase isoforms I and II

<p>Novel sulfonamide derivatives <b>6a</b>–<b>i</b>, as new carbonic anhydrase inhibitors which candidate for glaucoma treatment, were synthesized from the reactions of 4-amino-<i>N</i>-(4-sulfamoylphenyl) benzamide <b>4</b> and sulfonyl chloride derivatives <b>5a</b>–<b>i</b> with high yield (71–90%). The structures of these compounds were confirmed by using spectral analysis (FT-IR, ¹H NMR, ¹³C NMR, LC/MS and HRMS). The inhibition effects of <b>6a</b>–<b>i</b> on the hydratase and esterase activities of human carbonic anhydrase isoenzymes, hCA I and II, which were purified from human erythrocytes with Sepharose®4B-l-tyrosine-<i>p</i>-aminobenzene sulfonamide affinity chromatography, were studied as <i>in vitro</i>, and IC₅₀ and <i>K</i>_i values were determined. The results show that newly synthesized compounds have quite powerful inhibitory properties.</p

Preparation of Two Maleic Acid Sulfonamide Salts and Their Copper(II) Complexes and Antiglaucoma Activity Studies

Two novel proton transfer compounds (HAP)+(SAMAL)- and (HBI)+(SAMAL)-.H2O were obtained from (E)-4-oxo-4-(4-sulfamoylphenylamino)but-2-enoic acid (HSAMAL) and 2-aminopyridine (AP) or 1H-benzimidazole (BI), respectively. Copper(II) complexes of salts and of HSAMAL have also been prepared. They have been characterized by elemental, spectral, thermal analyses, magnetic measurement and molar conductivity. Human carbonic anhydrase isozymes (hCA I and hCA II) were purified from erythrocytes by using affinity chromatography as 84.40 and 188.71 fold, respectively. The inhibitory effects of synthesized compounds and acetazolamide (AAZ, control compound) on the hydratase and esterase activities of hCA isozymes have been studied as in vitro to find out their antiglaucoma potentials. The inhibition constant (Ki) values of the compounds were in the range of 0.18 ± 0.007 to 10.24 ± 0.014 µmol L-1 for hCA I, and 0.12 ± 0.004 to 130.11 ± 0.021 µmol L-1 for hCA II

Synthesis and Structural Studies of Proton Transfer Salt Between Benzimidazole and (E)-4-oxo-4-(4-sulfamoylphenylamino)but-2-enoic Acid and Their Transition Metal Complexes, and Investigation of Inhibition Properties on hCAI and hCA II Isoenzymes

Bu çalışmada, ilk olarak sülfanilamit (sa) ve maleik anhidritin (mal) tepkimesinden (E)-3-(4- sülfamoyilfenil)amino)büt-2-enoik asit (Hsamal) bileşiği sentezlenmiş ve sonra bu bileşiğin 2-aminopiridin (ap) ile proton transfer tuzu (Hapsamal) hazırlanmıştır. Bu tuzun Fe(II), Co(II), Ni(II) ve Zn(II) geçiş metal kompleksleri sentezlenmiştir. Proton transfer tuzlarının yapısı elementel analiz, 1H-NMR, 13C-NMR, FT-IR, UV-Vis metotları ile aydınlatılmıştır. Amorf halde elde edilen geçiş metal komplekslerinin yapıları ise elementel analiz, ICP-OES, FT-IR, UV-Vis, manyetik duyarlılık ve molar iletkenlik sonuçları dikkate alınarak önerilmiştir. Ayrıca, sentezlenen maddelerin insan eritrosit hCA I ve hCA II izoenzimleri üzerindeki inhibisyon etkilerini belirlemek üzere in vitro çalışmalar yapılmıştır. Yeni sentezlenen maddelerin izoenzimlerin esteraz aktivitesini inhibe ettiği tespit edilmiştir. Bu maddelerin inhibisyon değerlerinin kontrol bileşiği asetazolamid (AAZ) değerleri ile kıyaslanabilir büyüklükte olduğu tespit edilmiştir.In this study, first (E)-4-oxo-4-(4-sulfamoylphenylamino)but-2-enoic acid (Hsamal) have been synthesized from the reaction between sulfanilamide (sa) and maleic anhydride (mal) and second, proton transfer salt (Hapsamal) has been prepared from 2-aminopyridine (ap) and Hsamal. Four transition metal complexes [Fe(II), Co(II), Ni(II) and Zn(II)] of the salt have also been synthesized. The structure of proton transfer compounds have been proposed by using elemantal analysis, 1H-NMR, 13C-NMR, FT-IR, UV-Vis techniques. The structure of amorphous metal complexes have been proposed by using elemantal analysis, ICP-OES, FT-IR, UV-Vis, magnetic susceptibility and molar conductivity techniques. In addition, in vitro studies have been performed to determine the inhibition effects of synthesized compounds on human erythrocyte hCA I and hCA II isoenzymes. It has been observed that synthesized compounds have affected esterase activities of hCA I and hCA II and the inhibition values of these compounds are comparable with the inhibition values of control compound acetazolamide (AAZ)

Three-component synthesis and carbonic anhydrase inhibitory properties of novel octahydroacridines incorporating sulfaguanidine scaffold

<p>Novel sulfaguanidines incorporating acridine moiety were synthesized by the reaction of cyclohexane-1,3-dione, sulfaguanidine, and aromatic aldehydes. Synthesis of these compounds was performed in water at room temperature, and their structures were confirmed by using spectral analysis (IR, ¹H-NMR, ¹³C-NMR, and HRMS). Human carbonic anhydrase isoenzymes (hCA I and II) were purified from erythrocyte cells with affinity chromatography. hCA I was purified 83.40-fold with a specific activity, 1060.9 EU mg protein⁻¹, and hCA II was purified 262.32-fold with a specific activity, 3336.8 EU mg protein⁻¹. The inhibitory effects of newly synthesized sulfaguanidines and acetazolamide, (AAZ) as a control compound, on hydratase and esterase activities of these isoenzymes have been studied <i>in vitro</i>. Synthesized compounds have moderate inhibition potentials on hCA I and hCA II isoenzymes. IC₅₀ values of compounds for esterase activity are in the range of 118.4 ± 7.0 μM–257.5 ± 5.2 μM for hCA I and 86.7 ± 3.0 μM–249.4 ± 10.2 μM for hCA II, respectively.</p

Synthesis and characterization of Cu(II) complexes of 2-amino-6-sulfamoylbenzothiazole and their inhibition studies on carbonic anhydrase isoenzymes

WOS: 0004401257000232-Amino-6-sulfamoylbenzothiazole (SMABT) and its proton transfer compound (HSMABT)(+)(HDPC)(-) (1) with 2,6-pyridinedicarboxylic acid (H2DPC), and their Cu(II) complexes (2 of SMABT, 3 and 4 of 1) have been prepared and characterized by spectroscopic techniques. Additionally, single crystal X-ray diffraction techniques were applied to all complexes. All compounds, including acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibition effects on human hCA I and hCA II for their hydratase and esterase activities. The synthesized complexes have remarkable inhibitory effects on hCA I and hCA II isoenzymes. The inhibition potentials of the proton transfer salt (1) and the metal complexes (2-4) are comparable with AAZ. Esterase K-i values of the compounds (1-4) are in the range of 0.089 +/- 0.008 mu M-0.149 +/- 0.017 mu M for hCA I and 0.046 +/- 0.008 mu M-0.085 +/- 0.019 mu M for hCA II. Inhibition data have been analyzed by using a one-way analysis of variance for multiple comparisons (p < 0.0001). (C) 2018 Published by Elsevier Ltd.Dumlupinar University Research Fund [2014/18]; Aksaray University of Science and Technology Application and Research Center [2010K120480]The authors acknowledge the support provided by Dumlupinar University Research Fund (grant No. 2014/18). In addition, the authors acknowledge Aksaray University of Science and Technology Application and Research Center, for the use of the Bruker SMART BREEZE CCD diffractometer (purchased under grant No. 2010K120480 of the State of Planning Organization)

Synthesis and characterization of complexes of a novel proton transfer salt and their inhibition studies on carbonic anhydrase isoenzymes

A novel proton transfer compound (HClABT)(+)(HDPC.H2DPC)(-) (1) and its Fe(III), Co(II), Ni(II) and two different Cu(II) complexes (2-6) have been prepared and characterized by spectroscopic techniques. Additionally, single crystal X-ray diffraction techniques were applied to all complexes. All compounds, including acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibition effects on human hCA I and hCA II for their hydratase and esterase activities. Although there is no inhibition for hydratase activities, all compounds have inhibited the esterase activities of hCA I and II. The comparison of the inhibition studies of 1-6 to parent compounds, ClABT and H2DPC, indicates that 1-6 have superior inhibitory effects. The inhibition effects of 2-6 are also compared to the inhibitory properties of the simple metal complexes of ClABT and H2DPC, revealing an improved transfection profile. Data have been analysed by using a one-way analysis of variance for multiple comparisons