1. Academic Validation
  2. Synthesis of novel benzene bissulfonamides with carbonic anhydrase and choline esterase inhibitory properties

Synthesis of novel benzene bissulfonamides with carbonic anhydrase and choline esterase inhibitory properties

  • Bioorg Chem. 2025 Aug 31:165:108938. doi: 10.1016/j.bioorg.2025.108938.
Uğur Canoğlu 1 Akın Akıncıoğlu 2 Necla Öztaşkın 1 Ahmet Çağan 3 Rüya Sağlamtaş 4 Hülya Akıncıoğlu 5 Süleyman Göksu 6
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Atatürk University, 25240 Erzurum, Türkiye.
  • 2 Ağrı İbrahim Çeçen University, Central Researching Laboratory, 04100 Agri, Türkiye; Ağrı İbrahim Çeçen University, Vocational School, 04100 Agri, Türkiye.
  • 3 Ağrı İbrahim Çeçen University, Central Researching Laboratory, 04100 Agri, Türkiye.
  • 4 Ağrı İbrahim Çeçen University, Central Researching Laboratory, 04100 Agri, Türkiye; Agri Ibrahim Cecen University, Vocational School of Health Services, Medical Services and Techniques Department, 04100 Agri, Türkiye.
  • 5 Agri Ibrahim Cecen University, Faculty of Arts and Sciences, Chemistry Department, 04100 Agri, Türkiye.
  • 6 Department of Chemistry, Faculty of Science, Atatürk University, 25240 Erzurum, Türkiye. Electronic address: sgoksu@atauni.edu.tr.
Abstract

Compounds that possess a benzene sulfonamide structure are utilized in a wide range of fields. Benzene bissulfonamides are also important compounds in the field of organic and medicinal chemistry. Based on these features, a series of benzene bissulfonamides were synthesized in moderate yields starting from 3-methylanisole. The in vitro effects of novel benzene bissulfonamide derivatives on several significant metabolic Enzymes, including human Carbonic Anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), were systematically evaluated. The title compounds exhibited IC50 values ranging from 2.76 ± 0.40 to 265.48 ± 7.33 μM against hCA I and from 2.98 ± 0.49 to 313.92 ± 11.48 μM against hCA II, whereas the reference compound AZA demonstrated inhibition at the nanomolar level for both Enzymes. On the Other hand, the synthesized compounds exhibited IC50 values ranging from 6.67 ± 1.88 to 192.26 ± 10.42 μM against AChE, and from 76.50 ± 3.76 nM to 211.10 ± 14.62 μM against BChE. In contrast, the reference inhibitor Tacrine displayed markedly higher potency, with IC50 values of 123.65 ± 4.41 nM for AChE and 8.39 ± 0.28 nM for BChE. Notably, compounds 20 and 21 demonstrated significant BChE inhibitory activity, with IC50 values of 76.50 ± 3.76 nM and 112.53 ± 4.83 nM, respectively, suggesting that these compounds may serve as promising lead molecules for the development of selective BChE inhibitors. In this study, it was determined that compound 20 was 2301-fold BChE selective, compound 16 was 111-fold BChE selective and 21 was 64-fold BChE selective. In addition, 12 was determined to be 27-fold AChE selective than BChE. Furthermore, ADME and Induced-Fit Docking (IFD) simulations were conducted to elucidate the similarities of the drugs and the mechanisms of inhibition exhibited by the synthesized compounds. The synthesized species may significantly contribute to discovering new pharmaceutical agents for treating diseases such as Alzheimer's and glaucoma, which represent significant chronic global health concerns.

Keywords

AChE; Asymmetric sulfonamides; BChE; Benzene bissulfonamide; Benzene sulfonamide; hCA I; hCA II.

Figures
Products