Synthesis, characterization and molecular docking of some novel hydrazonothiazolines as urease inhibitors

• Published in: Bioorganic chemistry 2020-01, Vol.94, p.103404, Article 103404
• Main Authors: Shehzad, Muhammad Tariq, Khan, Ajmal, Islam, Muhammad, Halim, Sobia Ahsan, Khiat, Mohammed, Anwar, Muhammad U., Hussain, Javid, Hameed, Abdul, Pasha, Anam Rubbab, Khan, Farhan A., Al-Harrasi, Ahmed, Shafiq, Zahid
• Format: Article
• Language: English
• Subjects: Canavalia - enzymology; Crystal X-ray analysis; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Hydrazonothiazolines; Molecular docking; Molecular Docking Simulation; Molecular Structure; Spectroscopic techniques; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Urease - antagonists & inhibitors; Urease - metabolism; Urease inhibition
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.103404

[Display omitted] •New hydrazonothiazolines (3a-3v) were synthesized via cyclization of the appropriate thiosemicarbzaone.•Single crystal X-ray crystallography was performed for compounds 3n and 3v.•All compounds displayed potent urease inhibitory activity with IC50 values of 1.73–27.3 µM.•Structure-activity relationship was interpretatively discussed for all compounds.•Molecular docking studies were established to elucidate the binding energy and interaction. A series of new hydrazonothiazolines (3a-v) was obtained in good to excellent yields (79–96%) via cyclization of the appropriate thiosemicarbazones with phenacyl bromide. The targeted compounds were characterized by advanced spectroscopic techniques, such as FTIR, 1HNMR, 13CNMR and ESI-MS. The structure of compounds 3n and 3v was unambiguously confirmed by single crystal X-ray analysis. All compounds displayed enhanced inhibitory activity against urease enzyme with IC50 values in range of 1.73 ± 1.57–27.3 ± 0.655 μM when compared to standard thiourea (IC50 = 20.8 ± 0.75 µM). The structure-activity relationship studies demonstrated that the activity of this series is due the central thiazole ring that interacts with nickel atoms in the active site of urease enzyme. Moreover, molecular docking studies were carried out to investigate the binding mode of all active compounds and an inactive (3u) with the active site of the urease enzyme. The docking results are in complete agreement with the experimental finding.