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

• Published in: Chemistry & biodiversity Vol. 20; no. 6; pp. e202200886 - n/a
• Main Authors: Kekeçmuhammed, Hüseyin, Tapera, Michael, Aydoğdu, Ekrem, Sarıpınar, Emin, Aydin Karatas, Elanur, Mehtap Uc, Eda, Akyuz, Mesut, Tüzün, Burak, Gulcin, İlhami, Emin Bora, Rıfat, Özer İlhan, İlhan
• Format: Journal Article
• Language: English
• Published: Switzerland Wiley Subscription Services, Inc 01.06.2023
• Subjects: anticancer agent; Anticancer properties; Antineoplastic Agents - chemistry; Antitumor activity; Antitumor agents; Biological activity; Cancer; Carbonic Anhydrase I; Carbonic Anhydrase II; carbonic anhydrase inhibitors; Carbonic Anhydrase Inhibitors - chemistry; Carrier Proteins; Chemical synthesis; Cytotoxicity; Epilepsy; Glaucoma; hydrazone; Hydrazones; Hydrazones - pharmacology; Imidazole; Imidazoles - pharmacology; Isoforms; Mathematical analysis; Michael reaction; Molecular docking; Molecular Docking Simulation; Molecular Structure; Nerve Tissue Proteins; Nitroimidazoles; Prostate; Prostate cancer; Protein Isoforms - metabolism; Proteins; Spectral methods; Structure-Activity Relationship; synthesis; synthesis; carbonic anhydrase inhibitors; imidazole; hydrazone; anticancer agent
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.202200886

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.