2. Academic Validation
  3. 4-Oxycoumarinyl linked acetohydrazide Schiff bases as potent urease inhibitors

4-Oxycoumarinyl linked acetohydrazide Schiff bases as potent urease inhibitors

  • Bioorg Chem. 2020 Dec:105:104365. doi: 10.1016/j.bioorg.2020.104365.
Fouzia Naz 1,  Kanwal 1,  Mehreen Latif 2,  Uzma Salar 3,  Khalid Mohammed Khan 4,  Mariya Al-Rashida 5,  Irfan Ali 1,  Basharat Ali 1,  Muhammad Taha 6,  Shahnaz Perveen 7
Affiliations

Affiliations

  • 1 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
  • 2 Bahria University Medical and Dental College, Karachi 75270, Pakistan.
  • 3 Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
  • 4 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia. Electronic address: khalid.khan@iccs.edu.
  • 5 Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan.
  • 6 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
  • 7 PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
PMID: 33091669 DOI: 10.1016/j.bioorg.2020.104365
Abstract

Urease Enzyme is responsible to catalyze the hydrolysis of urea into carbamate and ammonia. Then carbamate hydrolyzed to ammonia and carbon dioxide. Excess release of ammonia leads to increase pH in stomach that actually encourages the survival of Helicobacter pylori. H. pylori involves in various disorders most commonly peptic ulcer, pyelonephritis, hepatic coma, kidney stone formation, urolithiasis, and encephalopathy. Apart from many pharmacological properties, coumarin and Schiff Bases are known to possess urease inhibitory activity. Therefore, these two pharmacologically important scaffolds are combined into single hybrid molecules to assess their potential as urease inhibitors. For this aim, N'-benzylidene-2-((2-oxo-2H-chromen-4-yl)oxy)acetohydrazide Schiff base derivatives 3-27 were synthesized by following a three step reaction strategy. Structures of all synthetic molecules were characterized by EI-MS, 1H-, and 13C NMR spectroscopic techniques. All molecules were assessed for urease inhibitory activity and found to possess a varying degree of inhibitory potential in the range of IC50 = 12.3 ± 0.69 to 88.8 ± 0.04 μM. Amongst the active analogs, compounds 7 (IC50 = 16.2 ± 0.11 μM), 9 (IC50 = 15.2 ± 0.14 μM), 10 (IC50 = 12.3 ± 0.69 μM), 12 (IC50 = 16.3 ± 0.45 μM), and 15 (IC50 = 17.6 ± 0.28 μM) were identified as potent inhibitors compared to standard urea (IC50 = 21.5 ± 0.47 μM). It is conferred from structure-activity relationship (SAR) that variation in inhibitory activity is due to different substitutions pattern on aryl ring. Moreover, molecular docking studies were carried out to understand the interactions of ligand with the active pocket of urease Enzyme.

Keywords

Chromene/coumarin; In silico; In vitro; Structure-activity relationship; Synthesis; Urease inhibitory activity.

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