Synthesis, Biological Activity Evaluation and Molecular Docking of Imidazole Derivatives Possessing Hydrazone Moiety

Kekecmuhammed H., Tapera M., Aydogdu E., SARIPINAR E., KARATAŞ E. A., Uc E. M., ...Daha Fazla

CHEMISTRY & BIODIVERSITY, cilt.20, sa.6, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 20 Sayı: 6
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/cbdv.202200886
  • Dergi Adı: CHEMISTRY & BIODIVERSITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: anticancer agent, carbonic anhydrase inhibitors, hydrazone, imidazole, synthesis, CARBONIC-ANHYDRASE, INHIBITORY PROPERTIES, ALPHA-GLYCOSIDASE, CRYSTAL-STRUCTURE, ACETYLCHOLINESTERASE, BUTYRYLCHOLINESTERASE, DESIGN
  • Atatürk Üniversitesi Adresli: Evet

Özet

In an attempt to identify potential active anticancer agents with low cytotoxic properties and CA inhibitors, a new series of hybrid compounds incorporating imidazole ring and hydrazone moiety as part of their structure were synthesized by aza-Michael addition reaction followed by intramolecular cyclization. The structure of synthesized compounds was elucidated using various spectral techniques. Synthesized compounds were evaluated for their in vitro anticancer (prostate cell lines; PC3) and CA inhibitory (hCA I and hCA II) activity. Among them, some compound displayed remarkable anticancer activity and CA inhibitory activity with K-i values in range of 17.53 +/- 7.19-150.50 +/- 68.87 nM against cytosolic hCA I isoform associated with epilepsy, and 28.82 +/- 14.26-153.27 +/- 55.80 nM against dominant cytosolic hCA II isoforms associated with glaucoma. Furthermore, the theoretical parameters of the bioactive molecules were calculated to establish their drug-likeness qualities. The proteins used for the calculations are prostate cancer protein (PDB ID: 3RUK and 6XXP). ADME/T analysis was carried out to examine the drug properties of the studied molecules.