Oxidation of cyanobenzocycloheptatrienes: Synthesis, photooxygenation reaction and carbonic anhydrase isoenzymes inhibition properties of some new benzotropone derivatives

Guney M., Coskun A., TOPAL F., DAŞTAN A., GÜLÇİN İ., SUPURAN C. T.

BIOORGANIC & MEDICINAL CHEMISTRY, cilt.22, sa.13, ss.3537-3543, 2014 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 13
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.bmc.2014.04.007
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.3537-3543
  • Anahtar Kelimeler: Benzocycloheptatriene, Benzotropone, Oxidation, Rearrangement, Nitrile-substituted drugs, Carbonic anhydrase inhibition, ERYTHROCYTE ISOZYMES I, SINGLET OXYGEN, ISOFORMS I, SULFONAMIDE DERIVATIVES, CYCLOADDITION REACTIONS, BICYCLIC ENDOPEROXIDES, ANTITUMOR AGENTS, ESTER ANALOGS, VITRO, ANTIOXIDANT
  • Atatürk Üniversitesi Adresli: Evet

Özet

The oxidation of some cyanocycloheptatrienes with CrO3 and pyridine was investigated and a few new nitrile functionalised benzotropone derivatives were obtained. Photooxygenation reaction of these products was also studied. The structures of the formed products were determined on the basis of NMR spectroscopy and the formation mechanism of unusual products was discussed. Human carbonic anhydrase isoenzymes I, and II (hCA I and hCA II) inhibition properties of nitrile functionalized new benzotropone derivatives were also studied. Both CA isozymes were inhibited in the low micromolar range by these nitrile functionalized benzotropone analogues. The newly synthesized benzotropone derivatives showed inhibition constants in the sub-micromolar range (2.51-4.06 mu M). The best hCA I inhibition was observed in 5H-benzocycloheptene-7-carbonitrile (K-1: 2.88 +/- 0.86 mu M). On the other hand, 5-oxo-5H-benzocycloheptatriene-7-carbonitrile showed the powerful inhibitory effect against hCA II (K-i: 2.51 +/- 0.34 mu M). (C) 2014 Elsevier Ltd. All rights reserved.