Carbonic anhydrase inhibitory activities of novel proton transfer salts and their Cu(II) complexes
Keywords:2-Amino-6-chlorobenzothiazole, N-(3/4-sulfamoylphenyl)maleamide acids, proton transfer salt, Cu(II) complexes, carbonic anhydrase inhibition
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.
(1) Jonckers, T. H. M.; Rouan, M. C.; Haché, G.; Schepens, W.; Hallenberger, S.; Baumeister, J.; Sasaki, J. C., Benzoxazole and benzothiazole amides as novel pharmacokinetic enhancers of HIV protease inhibitors. Bioorg. Med. Chem. Let. 2012, 22 (15), 4998–5002.
(2) Supuran, C. T.; Casini, A.; Mastrolorenzo A.; Scozzafava, A., COX-2 selective inhibitors, carbonic anhydrase inhibition and anticancer properties of sulfonamides belonging to this class of pharmacological agents. Mini-Rev. Med. Chem. 2004, 4(6), 625–632. https://doi.org/10.2174/1389557043403792
(3) Masini, E.; Carta, F.; Scozzafava, A.; Supuran C. T., Antiglaucoma carbonic anhydrase inhibitors: a patent review. Exp. Opin.Therap. Pat. 2013, 23(6), 705–716. https://doi.org/10.1517/13543776.2013.794788
(4) Chohan, Z. H.; Hassan, M.; Khan, M. K.; Supuran, C. T., In vitro antibacterial, antifungal and cytotoxic properties of sulfonamide-derived Schiff's bases and their metal complexes. J. Enz. Inh. Med Chem. 2005, 20(2), 183‒188.
(5) Scozzafava, A.; Owa, T.; Mastrolorenzo, A.; Supuran, C. T., Anticancer and antiviral sulfonamides. Curr. Med. Chem. 2003, 10(11), 925–953.
(6) Sentürk, M.; Alıcı, H. A.; Beydemir, Ş.; Küfrevioğlu, Ö. İ., In vitro and in vivo effects of some benzodiazepine drugs on human and rabbit erythrocyte carbonic anhydrase enzymes. J. Enz. Inh. Med Chem. 2012, 27(5), 680–684.
(7) Imran, S.; Taha, M.; Ismail, N. H.; Fayyaz, S.; Khan, K. M.; Choudhary, M. I., Synthesis of novel bisindolyl-methanes: New carbonic anhydrase II inhibitors: docking and 3D pharmacophore studies. Bioorg. Chem. 2016, 68, 90‒104.
(8) Bulli, I.; Dettori, I.; Coppi, E.; Cherchi, F.; Venturini, M.; Di Cesare Manelli, L.; Ghelardini, C.; Nocentini, A.; Supuran, C. T.; Pugliese, A. M.; Pedata, F., Role of carbonic anhydrase in cerebral ischemia and carbonic anhydrase inhibitors as putative protective agents. Inter. J. Mol. Sci. 2021, 22(9), 5029.
(9) Supuran, C. T., Structure and function of carbonic anhydrases. Biochem. J. 2016, 473(14), 2023–2032. https://doi.org/10.1042/BCJ20160115
(10) Sarikaya, B.; Ceruso, M.; Carta, F.; Supuran, C. T., Inhibition of carbonic anhydrase isoforms I.; II, IX and XII with novel Schiff bases, identification of selective inhibitors for the tumor-associated isoforms over the cytosolic ones. Bioorg. Med. Chem. 2014, 22(21), 5883–5890. https://doi.org/10.1016/j.bmc.2014.09.021
(11) Gao, B. B.; Clermont, A.; Rook, S.; Fonda, S. J.; Srini-vasan, V. J.; Wojtkowski, M.; Fujimoto, J. G.; Avery, R. L.; Arrigg, P. G.; Bursell, S. E.; Aiello, L. P.; Feener, E. P., Extracellular carbonic anhydrase mediates hem-orrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nat. Med. 2007, 13, 181‒188. https://doi.org/10.1038/nm1534
(12) Kumar, R.; Kumar, A.; Ram, S.; Angeli, A.; Bonardi, A.; Nocentini, A.; Gratteri, P.; Supuran, C. T.; Sharma, P. K., Novel benzenesulfonamide-bearing pyrazoles and 1,2,4-thiadiazoles as selective carbonic anhydrase inhibitors. Arc. der Phar. 2022, 355, e2100241.
(13) Pacchiano, F.; Carta, F.; McDonald, P. C.; Lou, Y.; Vullo, D.; Scozzafava, A.; Dedhar, S.; Supuran, C. T., Ureido-substituted benzenesulfonamides potently in-hibit carbonic anhydrase IX and show antimetastatic activity in a model of breast cancer metastasis. J. Med. Chem. 2011, 54(6), 1896–1902. https://doi.org/10.1021/jm101541x
(14) Téllez, F.; López-Sandoval, H.; Castillo-Blum, S. E.; Barba-Behrens, N., Coordination behavior of benzimidazole, 2-substituted benzimidazoles and benzothiazoles towards transition metal ions. Arkivoc 2008, (v), 245–275.
(15) İlkimen, H.; Tekşen, Y.; Yenikaya, C.; Turhan, İ.; Tunç, T.; Sarı, M., Synthesis, characterization and pharmaco-logical evaluation of the proton transfer salts of 2-aminobenzothiazole derivatives with 5-sulfosalicylic acid and their Cu(II) complexes. J. Coord. Chem. 2018, 71(16–18), 2831‒2842.
(16) İlkimen, H.; Yenikaya, C.; Sarı, M.; Bülbül, M.; Tun-ca, E.; Dal, H., Synthesis and characterization of a proton transfer salt between 2,6-pyridinedicarboxylic acid and 2-aminobenzothiazole and its complexes and their inhibition studies on carbonic anhydrase isoen-zymes. J. Enz. Inh. Med Chem. 2014, 29(3), 353–361.
(17) İlkimen, H.; Yenikaya, C.; Bülbül, M.; İmdat, G., Syn-thesis and characterization of proton transfer salt be-tween maleamic acid derivative including sulfonamide moiety and 2-aminopyridine and preparation of their Co(II) and Cu(II) complexes and investigation of inhi-bition properties on carbonic anhydrase isoenzymes. Celal Bayar Univ. J. Sci. 2017, 13(1), 211‒225.
(18) Yenikaya, C.; İlkimen, H.; Demirel, M. M.; Ceyhan, B.; Bülbül, M.; Tunca, E., Preparation of two maleic acid sulfonamide salts and their Cu(II) complexes and antiglaucoma activity studies. J. Braz. Chem. Soc. 2016, 27(10), 1706–1714.
(19) Yenikaya, C.; İlkimen, H.; Ceyhan, B.; Demirel, M. M.; Tunca, E.; Bülbül, M., Synthesis and structural studies of proton transfer salt between benzimidazole and (E)-3-(4-sulfamoylphenylcarbamoyl)acrylic acid and their transition metal complexes, and investigation of their inhibition properties. Sakarya Univ. J. Sci. 2017, 21(3), 454–462. https://doi.org/10.16984/saufenbilder.221276
(20) Kremlev, M. M.; Kul'chitskaya, N. E.; Biba, A. D.; Romanenko, V. D., Arenesulfonamides. XXVII. N-(sulfamoylaryl)maleimides. Khim. Tekh. 1971, 21, 5–10.
(21) Bergmann, F.; Schapiro, D., Further acylation experi-ments with sulfanilamide and heterocyclic amines. J. Org. Chem. 1942, 7(5), 419‒423.
(22) Misra, R. P.; Mahapatra, B. B.; Guru, S., Cobalt(II) and copper(II) complexes with substituted aminobenzo-thiazoles. Part II. Journal of the Indian Chemical Soc. 1981, 58(8), 808–810.
(23) Rickli, E. E.; Ghazanfar, S. A.; Gibbson, B. H.; Edsall, J. T., Carbonic anhydrases from human erythrocytes: Preparation and properties of two enzymes. J. Bio. Chem. 1964, 239(4), 1065–1078.
(24) Bradford, M. M., A rapid and sensitive method for the quantitation of microgram quantities of protein utiliz-ing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248‒254.
(25) Laemmli, U. K., Cleavage of structural proteins during the assembly of the head of Bacteriophage T4. Nature 1970, 22, 680–685. https://doi.org/10.1038/227680a0
(26) Wilbur, K. M.; Anderson, N. G., Electrometric and colorimetric determination of carbonic anhydrase. J. Bio. Chem. 1948, 176, 147–154.
(27) Verpoorte, J. A.; Mehta, S.; Edsall, J. T. Esterase activ-ities of human carbonic anhydrases B and C. J. Bio. Chem. 1967, 242, 4221–4229.
(28) Lineweaver, H.; Burk, D., The determination of en-zyme dissociation constants. J. Am. Chem. Soc. 1934, 56(3), 658–666. https://doi.org/10.1021/ja01318a036
(29) Geary, W. J., The use of conductivity measurements in organic solvents for the characterisation of coordination compounds. Coord. Chem. Rev. 1971, 7, 81‒121. https://doi.org/10.1016/S0010-8545(00)80009-0
(30) Alterio, V.; Di Fiore, A.; D’Ambrosio, K.; Supuran, C. T.; De Simone, G., Multiple binding modes of inhibitors to carbonic anhydrase: How to design specific drugs targeting 15 different isoforms? Chem. Rev. 2012, 112, 4421‒4468. https://doi.org/10.1021/cr200176r
(31) Tanpure, R. P.; Ren, B; Peat, T. S.; Bornaghi, R. F.; Vullo, D.; Supuran, C. T.; Poulsen, S. A., Carbonic anhydrase inhibitors with dual-tail moieties to match the hydrophobic and hydrophilic halves of the carbon-ic anhydrase active site. J. Med. Chem. 2015, 58(3), 1494–1501. https://doi.org/10.1021/jm501798g
(32) Tawfik, H. O.; Petreni, A.; Supuran, C. T.; El-Hamamsy, M. H., Discovery of new carbonic anhy-drase IX inhibitors as anticancer agents by toning the hydrophobic and hydrophilic rims of the active site to encounter the dual-tail approach. Euro. J. Med. Chem. 2022, 232, 114190.
- 2023-07-01 (2)
- 2023-05-30 (1)
How to Cite
Copyright (c) 2023 Halil Ilkimen, Yasemin Tunca, Ekrem Tunca, Metin Bülbül, Cengiz Yenikaya
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The authors agree to the following licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material
- for any purpose, even commercially.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- NonCommercial — You may not use the material for commercial purposes.