Cholinesterases, carbonic anhydrase inhibitory properties and in silico studies of novel substituted benzylamines derived from dihydrochalcones

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Akincioglu A., Göksu S., Naderi A., Akincioglu H., Kılınç N., Gülçin İ.

COMPUTATIONAL BIOLOGY AND CHEMISTRY, cilt.94, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 94
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.compbiolchem.2021.107565
  • Dergi Adı: COMPUTATIONAL BIOLOGY AND CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, Computer & Applied Sciences, EMBASE, INSPEC, MEDLINE, zbMATH
  • Anahtar Kelimeler: Dihydrochalcones, Sulfamides, Ureas, Carbonic anhydrase, Acetylcholinesterase, Butyrylcholinesterase, N, N-Dipropargylbenzylamines, CRYSTAL-STRUCTURE, BIOLOGICAL EVALUATION, ALZHEIMERS-DISEASE, ACETYLCHOLINESTERASE, ANTIOXIDANT, DERIVATIVES, ENZYME, POTENT, UREAS, VITRO
  • Atatürk Üniversitesi Adresli: Evet

Özet

A series of novel urea, sulfamide and N,N-dipropargyl substituted benzylamines were synthesized from dihydrochalcones. The synthesized compounds were evaluated for their cholinesterases and carbonic anhydrase inhibitory actions. The known dihydrochalcones were converted into four new benzylamines via reductive amination. N,N-Dipropargylamines, ureas and sulfamides were synthesized following the reactions of benzylamines with propargyl bromide, N,N-dimethyl sulfamoyl chloride and N,N-dimethyl carbamoyl chloride. The novel substituted benzylamines derived from dihydrochalcones were evaluated against some enzymes such as human erythrocyte carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The novel substituted benzylamines derived from dihydrochalcones exhibited Ki values in the range of 0.121-1.007 nM on hCA I, and 0.077-0.487 nM on hCA II closely related to several pathological processes. On the other hand, Ki values were found in the range of 0.112-0.558 nM on AChE, 0.061-0.388 nM on BChE. As a result, novel substituted benzylamines derived from dihydrochalcones showed potent inhibitory profiles against indicated metabolic enzymes. In addition, Induced-Fit Docking (IFD) simulations and ADME prediction studies have also been carried out to elucidate the inhibition mechanisms and druglikeness of the synthesized compounds. Therefore, these results can make significant contributions to the treatment of some global diseases, especially Alzheimer's diseases and glaucoma, and the development of new drugs.