Synthesis of 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene Derivatives and Evaluations of Their Carbonic Anhydrase Isoenzymes Inhibitory Effects

ARTUNC T., ÇETİNKAYA Y., GOCER H., GÜLÇİN İ., MENZEK A., ŞAHİN E., ...Daha Fazla

CHEMICAL BIOLOGY & DRUG DESIGN, cilt.87, sa.4, ss.594-607, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 87 Sayı: 4
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1111/cbdd.12695
  • Dergi Adı: CHEMICAL BIOLOGY & DRUG DESIGN
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.594-607
  • Anahtar Kelimeler: Aldol condensation, bromination, carbonic anhydrase, cyclopentenyl, enzyme inhibition, Friedel-Crafts reaction, INCORPORATING 1,3,5-TRIAZINE MOIETIES, TROUT ONCORHYNCHUS-MYKISS, ERYTHROCYTES IN-VITRO, ISOFORMS I, BENZENE SULFONAMIDES, ANTIOXIDANT PROPERTIES, ISOZYME-IX, BROMOPHENOLS, XII, (3,4-DIHYDROXYPHENYL)(2,3,4-TRIHYDROXYPHENYL)METHANONE
  • Atatürk Üniversitesi Adresli: Evet

Özet

Rearrangement of 1,6-bis(3,4-dimethoxyphenyl)hexane-1,6-dione (8) gave two isomeric products having cyclopentene moiety. Starting from the major product (3,4-dimethoxyphenyl)[2-(3,4-dimethoxyphenyl)cyclopent-1-en-1-yl]methanone (11), eight new compounds (16-23) were obtained by the reactions such as reduction (by catalytic hydrogenation and NaBH4), nitration, 1,4-addition, bromination, and esterification reactions. Carbonic anhydrases (CA, E.C.4.2.1.1) are ubiquitous metalloenzymes present in almost all living organism that catalyze a simple reaction, the conversion of carbon dioxide (CO2) and water (H2O) to bicarbonate ion (HCO3-) and a proton (H+). CA isoenzymes I and II (hCA I and II) inhibition effects of synthesized eleven new and four known compounds (8-13 and 15-23) were investigated. Inhibition studies of the hCA I and II with 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene derivatives revealed that they possess effective inhibitory potency. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene derivatives with K(i)s in the range of 313.16-1537.00 nm against hCA I and in the range of 228.31-1927.31 nm against hCA II, respectively.