ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

Ekrem Tunca, Metin Bülbül, Halil İlkimen, Rukiye Saygılı Canlıdinç, and Cengiz Yenikaya

Department of Biochemistry, Faculty of Arts and Sciences, Kütahya Dumlupınar University, Kütahya, Turkey

E-mail: ekrem.tunca@dpu.edu.tr

Received: 8 August 2019  Accepted: 27 January 2020

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 (21–26) 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).

Keywords: Cancer; Carbonic anhydrase; 5-Sulfosalicylic acid; 2-Aminopyridine; Proton transfer salt; Metal complex

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-020-01078-5

Chemical Papers 74 (7) 2365–2374 (2020)