Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase

YILMAZ S., AKBABA Y., ÖZGERIŞ B., KOSE L. P., GÖKSU S., GÜLÇİN İ., ...Daha Fazla

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.31, sa.6, ss.1484-1491, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31 Sayı: 6
  • Basım Tarihi: 2016
  • Doi Numarası: 10.3109/14756366.2016.1149477
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1484-1491
  • Anahtar Kelimeler: Acetylcholinesterase, carbamates, carbonic anhydrase, enzyme inhibition, synthesis, TROUT ONCORHYNCHUS-MYKISS, ERYTHROCYTES IN-VITRO, ISOENZYMES HCA I, SULFONAMIDE DERIVATIVES, PHENOLIC-COMPOUNDS, ENZYME-ACTIVITY, ISOZYMES I, ISOFORMS I, ANTIOXIDANT, SULFAMIDES
  • Atatürk Üniversitesi Adresli: Evet

Özet

A series of carbamate derivatives were synthesized and their carbonic anhydrase I and II isoenzymes and acetylcholinesterase enzyme (AChE) inhibitory effects were investigated. All carbamates were synthesized from the corresponding carboxylic acids via the Curtius reactions of the acids with diphenyl phosphoryl azide followed by addition of benzyl alcohol. The carbamates were determined to be very good inhibitors against for AChE and hCA I, and II isoenzymes. AChE inhibition was determined in the range 0.209-0.291 nM. On the other hand, tacrine, which is used in the treatment of Alzheimer's disease possessed lower inhibition effect (K-i: 0.398 nM). Also, hCA I and II isoenzymes were effectively inhibited by the carbamates, with inhibition constants (Ki) in the range of 4.49-5.61 nM for hCA I, and 4.94-7.66 nM for hCA II, respectively. Acetazolamide, which was clinically used carbonic anhydrase (CA) inhibitor demonstrated Ki values of 281.33 nM for hCA I and 9.07nM for hCA II. The results clearly showed that AChE and both CA isoenzymes were effectively inhibited by carbamates at the low nanomolar levels.