Synthesis of benzamide derivatives with thiourea-substituted benzenesulfonamides as carbonic anhydrase inhibitors

TUĞRAK M., GÜL H. İ., Demir Y., GÜLÇİN İ.

ARCHIV DER PHARMAZIE, cilt.354, sa.2, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 354 Sayı: 2
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/ardp.202000230
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: benzamide, carbonic anhydrase, enzyme inhibitors, sulfonamides, thiourea, BIOLOGICAL EVALUATION, SULFONAMIDE DERIVATIVES, MANNICH-BASES, POTENT, IX, DISCOVERY, DOCKING, DESIGN
  • Atatürk Üniversitesi Adresli: Evet

Özet

The novel compounds with the chemical structure ofN-({4-[N '-(substituted)sulfamoyl]phenyl}carbamothioyl)benzamide (1a-g) and 4-fluoro-N-({4-[N '-(substituted)sulfamoyl]phenyl}carbamothioyl)benzamide (2a-g) were synthesized as potent and selective human carbonic anhydrase (hCA) I and hCA II candidate inhibitors. The aryl part was changed to sulfacetamide, sulfaguanidine, sulfanilamide, sulfathiazole, sulfadiazine, sulfamerazine, and sulfametazine. TheK(i)values of compounds1a-gwere in the range of 20.73 +/- 4.32 to 59.55 +/- 13.07 nM (hCA I) and 5.69 +/- 0.43 to 44.81 +/- 1.08 nM (hCA II), whereas theK(i)values of compounds2a-gwere in the range of 13.98 +/- 2.57 to 75.74 +/- 13.51 nM (hCA I) and 8.15 +/- 1.5 to 49.86 +/- 6.18 nM (hCA II). Comparing theK(i)values of the final compounds and acetazolamide, compound1cwith the sulfanilamide moiety (K-i = 5.69 +/- 0.43 nM, 8.8 times) and2fwith the sulfamerazine moiety (K-i = 8.15 +/- 1.5 nM, 6.2 times) demonstrated promising and selective inhibitory effects against the hCA II isoenzyme, the main target protein in glaucoma. Furthermore, compounds1d(K-i = 20.73 +/- 4.32, 4 times) and2d(K-i = 13.98 +/- 2.57, 5.9 times), which have the sulfathiazole moiety, were found as potent hCA I inhibitors. Compounds1cand2fcan be considered as the lead compounds determined in the present study, which can be investigated further to alleviate glaucoma symptoms.