A novel and one-pot synthesis of new 1-tosyl pyrrol-2-one derivatives and analysis of carbonic anhydrase inhibitory potencies

ALP C., Ekinci D., Gultekin M. S., SENTURK M., ŞAHİN E., KÜFREVİOĞLU Ö. İ.

BIOORGANIC & MEDICINAL CHEMISTRY, cilt.18, sa.12, ss.4468-4474, 2010 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 18 Sayı: 12
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1016/j.bmc.2010.04.072
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.4468-4474
  • Anahtar Kelimeler: Carbonic anhydrase, 1-Tosyl-1H-pyrrol-2(5H)-one, 5-Hydroxy-1-tosyl-1H-pyrrol-2(5H)-one, hCA I, hCA II, Enzyme inhibitor, RAY CRYSTALLOGRAPHIC STRUCTURE, IN-VITRO INHIBITION, HUMAN ISOZYME-II, ESTERASE-ACTIVITIES, SULFONAMIDES, THIOXOLONE, PHENOLS, BINDING, SERIES, ADDUCT
  • Atatürk Üniversitesi Adresli: Evet

Özet

Here we propose a novel one-pot synthesis of new tosyl-pyrrole derivatives. By means of the new developed method, pyrrole derivatives were synthesized at room temperature in a single step, and a useful method is proposed for the synthesis of similar compounds. Moreover, inhibitions of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II by 1-tosyl-pyrrole and 1-tosyl-pyrrol-2-on derivatives were investigated. 1-Tosyl-pyrrole, 1-tosyl-1H-pyrrol-2(5H)-one, 5-hydroxy-1-tosyl-1H-pyrrol-2(5H)-one and 5-oxo-1-tosyl-2,5-dihydro-1H-pyrrol-2-yl acetate showed inhibitory action with K-i values in the range of 14.6-42.4 mu M for hCA I and 0.53-37.5 mu M for hCA II, respectively. All pyrrole derivatives were competitive inhibitors with 4-nitrophenylacetate as substrate. Some new synthesized pyrrole derivatives showed very effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors targeting other CA isoforms. (C) 2010 Elsevier Ltd. All rights reserved.