Synthesis and biological evaluation of bromophenol derivatives with cyclopropyl moiety: Ring opening of cyclopropane with monoester

BOZTAS M., TASLIMI P., YAVARİ M. A., GÜLÇİN İ., ŞAHİN E., MENZEK A.

BIOORGANIC CHEMISTRY, cilt.89, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 89
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.bioorg.2019.103017
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: Acetylcholinesterase, Bromination, Bromophenol, Carbonic anhydrase, Cyclopropane, Enzyme inhibition, ANHYDRASE INHIBITORY PROPERTIES, POTENT CARBONIC-ANHYDRASE, INCLUDING NATURAL-PRODUCTS, TROUT ONCORHYNCHUS-MYKISS, CRYSTAL-STRUCTURE, ISOENZYMES I, CYCLOHEXANONYL BROMOPHENOL, CYCLOADDITION REACTIONS, ANTIOXIDANT ACTIVITY, ALPHA-GLYCOSIDASE
  • Atatürk Üniversitesi Adresli: Evet

Özet

Trans-(1R*,2R*,3R*)-Ethyl 2-(3,4-dimethoxyphenyl)-3-methylcyclopropane-1-carboxylate (6) and its cis isomer 7 were obtained from the reaction of the methyl isoeugenol (5) with ethyl diazoacetate. The reduction and bromination reactions of the ester 6 and 7 together with the hydrolysis of all esters were carried out. Opening ring of cyclopropane was observed in the reaction of 7 with bromine. The opening of cyclopropane ring with COOR and synthesis of esters, alcohols and acids (6-26) are new. These obtained bromophenol derivatives (6-26) were effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms (hCA I and II) and acetylcholinesterase (AChE) enzymes with Ki values in the range of 7.8 +/- 0.9-58.3 +/- 10.3 nM for hCA I, 43.1 +/- 16.7-150.2 +/- 24.1 nM for hCA II, and 159.6 +/- 21.9-924.2 +/- 104.8 nM for AChE, respectively. Acetylcholinesterase inhibitors are the most popular drugs applied in the treatment of diseases such as Alzheimer's disease, Parkinson's disease, senile dementia, and ataxia, among others.