Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Investigation of the effects of the proton transfer salts of 2-aminopyridine derivatives with 5-sulfosalicylic acid and their Cu(II) complexes on cancer-related carbonic anhydrases: CA IX and CA XII

  • 19 Accesses

Abstract

Six novel proton transfer compounds (15–20) obtained from 5-sulfosalicylic acid (1) and 2-aminopyridine derivatives [2-amino-3-benzyloxypyridine (2), 2-amino-3-hydroxylpyridine (3), 2-amino-3-methylpyridine (4), 2-amino-3-nitropyridine (5), 2-amino-3-nitro-4-methylpyridine (6) and 2-amino-3-nitro-6-methylpyridine (7)] and their Cu(II) complexes (2126) along with the Cu(II) complexes of 2–7 (9–14) have been prepared and characterized by spectroscopic techniques. The in vitro inhibition effects of all compounds on CA IX and CA XII isozymes as well as on hCA I and hCA II were investigated and the results were compared. The inhibition studies showed that the synthesized compounds are more selective to CA XII isozyme. The hydratase IC50 values of the compounds were determined as in the range of 15.61 ± 2.32 µM–99.02 ± 4.99 µM for hCA I, 22.36 ± 0.75 µM–77.03 ± 4.03 µM for hCA II, 23.90 ± 1.67 µM–138.63 ± 5.45 µM for CA IX, and 9.50 ± 1.16 µM–693.15 ± 8.96 µM for CA XII. The inhibition data have been analyzed using one-way analysis of variance for multiple comparisons (p < 0.0001).

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. Aggarwal M, Boone CD, Kondeti B, McKenna R (2013) Structural annotation of human carbonic anhydrases. J Enzyme Inhib Med Chem 28(2):267–277. https://doi.org/10.3109/14756366.2012.737323

  2. Bayram E, Şentürk M, Küfrevioğlu Öİ, Supuran CT (2008) In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. Bioorg Med Chem 16(20):9101–9105. https://doi.org/10.1016/j.bmc.2008.09.028

  3. Bennewith KL, Dedhar S (2011) Targeting hypoxic tumour cells to overcome metastasis. BMC Cancer 11:504. https://doi.org/10.1186/1471-2407-11-504

  4. Bild AH, Yao G, Chang JT, Wang Q, Potti A, Chasse D, Joshi MB, Harpole D, Lancaster JM, Berchuck A, Olson JA, Marks JR, Dressman HK, West M, Nevins JR (2006) Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 439:353–357. https://doi.org/10.1038/nature04296

  5. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1016/0003-2697(76)90527-3

  6. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT (2010) Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem 53:5511–5522. https://doi.org/10.1021/jm1003667

  7. Casey JR, Morgan PE, Vullo D, Scozzafava A, Mastrolorenzo A, Supuran CT (2004) Carbonic anhydrase inhibitors. Design of selective, membrane-impermeant inhibitors targeting the human tumor-associated isozyme IX. J Med Chem 47:2337–2347. https://doi.org/10.1021/jm031079w

  8. Cook D (1961) Vibrational spectra of pyridinium salts. Can J Chem 39(10):2009–2024. https://doi.org/10.1139/v61-271

  9. DeVita VT, Chu E (2008) A history of cancer chemotherapy. Cancer Res 68:8643–8653. https://doi.org/10.1158/0008-5472.CAN-07-6611

  10. Dubois L, Peeters S, Lieuwes NG, Geusens N, Thiry A, Wigfield S, Carta F, McIntyre A, Scozzafava A, Dogné JM, Supuran CT, Harris AL, Masereel B, Lambin P (2011) Specific inhibition of carbonic anhydrase IX activity enhances the in vivo therapeutic effect of tumor irridation. Radiother Oncol 99:424–431. https://doi.org/10.1016/j.radonc.2011.05.045

  11. Geary WJ (1971) The use of conductivity measurements in organic solvents for the characterisation of coordination compounds. Coord Chem Rev 7:81–122. https://doi.org/10.1016/S0010-8545(00)80009-0

  12. Gieling RG, Babur M, Mamnani L, Burrows N, Telfer BA, Carta F, Winum JY, Scozzafava A, Supuran CT, Williams KJ (2012) Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast carcinoma xenografts. J Med Chem 55:5591–5600. https://doi.org/10.1021/jm300529u

  13. International Agency for Research on Cancer (2014). World Cancer Report 2014. https://www.iarc.fr/cards_page/world-cancer-report/ Accessed 20 Apr 2018

  14. Khadikar PV, Joshi S, Kashkhedikar SG, Heda BD (1984) Metal-complexes of 5-sulphosalicylic acid and their antimicrobial activity. Indian J Pharm Sci 46(6):209–211

  15. Khadikar PV, Ali SM, Pol B, Heda BD (1986) Effect of metal ions on the antimicrobial activity of 5-sulphosalicylic acid. Acta Microbiol Hung 33(2):97–102

  16. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685. https://doi.org/10.1038/227680a0

  17. Lou Y, McDonald PC, Oloumi A, Chia S, Ostlund C, Ahmadi A, Kyle A, Auf dem Keller U, Leung S, Huntsman D, Clarke B, Sutherland BW, Waterhouse D, Bally M, Roskelley C, Overall CM, Minchinton A, Pacchiano F, Carta F, Scozzafava A, Touisni N, Winum JY, Supuran CT, Dedhar S (2011) Targeting tumor hypoxia: suppression of breast tumor growth and metastasis by novel carbonic anhydrase IX inhibitors. Cancer Res 71:3364–3376. https://doi.org/10.1158/0008-5472.CAN-10-4261

  18. Luisi G, Angelini G, Gasbarri C, Laghezza A, Agamennone M, Loiodice F, Supuran CT, Campestre C, Tortorella P (2017) Dual targeting of cancer-related human matrix metalloproteinases and carbonic anhydrases by chiral N-(biarylsulfonyl)-phosphonic acids. J Enzyme Inhib Med Chem 32(1):1260–1264. https://doi.org/10.1080/14756366.2017.1378192

  19. McDonald PC, Winum JY, Supuran CT, Dedhar S (2012) Recent developments in targeting carbonic anhydrase IX for cancer therapeutics. Oncotarget 3:84–97. https://doi.org/10.18632/oncotarget.422

  20. Mohindru A, Fisher JM, Rabinovitz M (1983) Bathocuproine sulphonate: a tissue culture-compatible indicator of copper-mediated toxicity. Nature 303:64–65. https://doi.org/10.1038/303064a0

  21. Nakamoto K (1997) Infrared and raman spectra of inorganic and coordination compounds. Interscience-Wiley, NewYork

  22. Neri D, Supuran CT (2011) Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov 10:767–777. https://doi.org/10.1038/nrd3554

  23. Pacchiano F, Carta F, McDonald PC, Lou Y, Vullo D, Scozzafava A, Dedhar S, Supuran CT (2011) Ureido-substituted benzenesulfonamides potently inhibit carbonic anhydrase IX and show antimetastatic activity in a model of breast cancer metastasis. J Med Chem 54:1896–1902. https://doi.org/10.1021/jm101541x

  24. Pastorekova S, Parkkila S, Zavada J (2006) Tumor-associated carbonic anhydrases and their clinical significance. Adv Clin Chem 42:167–216. https://doi.org/10.1016/S0065-2423(06)42005-9

  25. Rami M, Dubois L, Parvathaneni NK, Alterio V, van Kuijk SJA, Monti SM, Lambin P, De Simone G, Supuran CT, Winum JY (2013) Hypoxia-targenting carbonic anhydrase IX inhibitors by a new series of nitroimidazole-sulfonamides/sulfamides/sulfamates. J Med Chem 56:8512–8520. https://doi.org/10.1021/jm4009532

  26. Rickli EE, Ghazanfar SAS, Gibbons BH, Edsall JT (1964) Carbonic anhydrases from erythrocytes. Preparation and properties of two enzymes. J Biol Chem 239:1065–1078

  27. Ruddon RW (2007) Cancer biology. Oxford University Press, New York

  28. Scozzafava A, Briganti F, Ilies MA, Supuran CT (2000) Carbonic anhydrase inhibitors: Synthesis of membrane-impermeant low molecular weight sulfonamides possessing in vivo selectivity for the membrane-bound versus cytosolic isozymes. J Med Chem 43:292–300. https://doi.org/10.1021/jm990479+

  29. Spacu G, Voichescu P (1936) Beiträge zum Studium der Ammoniakate einfacher Salze. (Tensimetrische Untersuchungen). I. Ammoniakate der Kupfersalze. Z Anorg Allg Chem 226(3):273–288. https://doi.org/10.1002/zaac.19362260306

  30. Supuran CT (2008) Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 7:168–181. https://doi.org/10.1038/nrd2467

  31. Tars K, Vullo D, Kazaks A, Leitans J, Lends A, Grandane A, Zalubovskis R, Scozzafava A, Supuran CT (2013) Sulfocoumarins (1,2-benzoxathiine-2,2-dioxides): a class of potent and isoform-selective inhibitors of tumor-associated carbonic anhydrases. J Med Chem 56:293–300. https://doi.org/10.1021/jm301625s

  32. Teo RD, Hwang JY, Termini J, Gross Z, Gray HB (2017) Fighting cancer with corroles. Chem Rev 117:2711–2729. https://doi.org/10.1021/acs.chemrev.6b00400

  33. Touisni N, Maresca A, McDonald PC, Lou Y, Scozzafava A, Dedhar S, Winum JY, Supuran CT (2011) Glycosyl coumarin carbonic anhydrase IX and XII inhibitors strongly attenuate the growth of primary breast tumors. J Med Chem 54:8271–8277. https://doi.org/10.1021/jm200983e

  34. Verpoorte JA, Mehta S, Edsall JT (1967) Esterase activities of human carbonic anhydrases B and C. J Biol Chem 242:4221–4229

  35. Wilbur KM, Anderson NG (1948) Electrometric and colorimetric determination of carbonic anhydrase. J Biol Chem 176:147–154

  36. Wilson WR, Hay MP (2011) Targeting hypoxia in cancer therapy. Nat Rev Cancer 11:393–410. https://doi.org/10.1038/nrc3064

  37. Yenikaya C, Sarı M, İlkimen H, Bülbül M, Büyükgüngör O (2011) Synthesis and characterization of a novel amino salicylate salt and its Cu(II) complex and their inhibition studies on carbonic anhydrase isoenzymes. Polyhedron 30:535–541. https://doi.org/10.1016/j.poly.2010.11.024

  38. Yenikaya C, İlkimen H, Demirel MM, Ceyhan B, Bülbül M, Tunca E (2016) Preparation of two maleic acid sulfonamide salts and their copper(II) complexes and antiglaucoma activity studies. J Brazil Chem Soc 27(10):1706–1714. https://doi.org/10.5935/0103-5053.20160051

Download references

Acknowledgements

This work was supported by Kütahya Dumlupınar University Research Fund (Grant No. 2015-49 and 2016-72).

Author information

Correspondence to Ekrem Tunca.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1827 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tunca, E., Bülbül, M., İlkimen, H. et al. Investigation of the effects of the proton transfer salts of 2-aminopyridine derivatives with 5-sulfosalicylic acid and their Cu(II) complexes on cancer-related carbonic anhydrases: CA IX and CA XII. Chem. Pap. (2020). https://doi.org/10.1007/s11696-020-01078-5

Download citation

Keywords

  • Cancer
  • Carbonic anhydrase
  • 5-Sulfosalicylic acid
  • 2-Aminopyridine
  • Proton transfer salt
  • Metal complex