Synthesis and in silico studies of triazene-substituted sulfamerazine derivatives as acetylcholinesterase and carbonic anhydrases inhibitors

BİLGİNER S., GÜL H. İ., ANIL B., Demir Y., GÜLÇİN İ.

ARCHIV DER PHARMAZIE, cilt.354, sa.1, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 354 Sayı: 1
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/ardp.202000243
  • 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: acetylcholinesterase, carbonic anhydrase, diazonium salt, molecular docking, sulfamerazine, triazene, BIOLOGICAL EVALUATION, ALZHEIMERS-DISEASE, MANNICH-BASES, HCA I, ISOENZYMES I, ANTICANCER, SULFONAMIDES, HYPOTHESIS, SULFAMIDES, POTENT
  • Atatürk Üniversitesi Adresli: Evet

Özet

A novel series of sulfonamides, 4-(3-phenyltriaz-1-en-1-yl)-N-(4-methyl-2-pyrimidinyl)benzenesulfonamides (1-9), was designed and synthesized by the diazo reaction between sulfamerazine and substituted aromatic amines for the first time. Their chemical structures were characterized by(1)H nuclear magnetic resonance (NMR),C-13 NMR, and high-resolution mass spectra. The newly synthesized compounds were evaluated in terms of acetylcholineasterase (AChE) and human carbonic anhydrases (hCA) I and II isoenzymes inhibitory activities. According to the AChE inhibition results, theK(i)values of the compounds1-9were in the range of 19.9 +/- 1.5 to 96.5 +/- 20.7 nM against AChE. Tacrine was used as the reference drug and itsK(i)value was 49.2 +/- 2.7 nM against AChE. TheK(i)values of the compounds1-9were in the range of 10.2 +/- 2.6 to 101.4 +/- 27.8 nM against hCA I, whereas they were 18.3 +/- 4.4 to 48.1 +/- 4.5 nM against hCA II. Acetazolamide was used as a reference drug and itsK(i)values were 72.2 +/- 5.4 and 52.2 +/- 5.7 nM against hCA I and hCA II, respectively. The most active compounds,1(nonsubstituted) against AChE,5(4-ethoxy-substituted) against hCA I, and8(4-bromo-substituted) against hCA II, were chosen and docked at the binding sites of these enzymes to explain the inhibitory activities of the series. The newly synthesized compounds presented satisfactory pharmacokinetic properties via the estimation of ADME properties.