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

Kekeçmuhammed H., Tapera M., Aydoğdu E., SARIPINAR E., Aydin Karatas E., Mehtap Uc E., ...Daha Fazla

Chemistry and 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 and 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
  • Sivas Cumhuriyet 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 Ki 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.