Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors.

A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also inve...

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Publicado en:BioMed Research International pp. 1 - 12
Autores principales: Rashid, Muhammad, Rafique, Hummera, Roshan, Sadia, Shamas, Shazia, Iqbal, Zafar, Ashraf, Zaman, Abbas, Qamar, Hassan, Mubashir, Qureshi, Zia Ur Rahman, Asad, Muhammad Hassham Hassan Bin
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 12/24/2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 12/24/2020
      pid: 480
      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        147770261
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        10.1155/2020/8867407
        147770261
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      ppct: 11
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        atl: Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors.
      aug:
        au:
          Rashid, Muhammad
          Rafique, Hummera
          Roshan, Sadia
          Shamas, Shazia
          Iqbal, Zafar
          Ashraf, Zaman
          Abbas, Qamar
          Hassan, Mubashir
          Qureshi, Zia Ur Rahman
          Asad, Muhammad Hassham Hassan Bin
        affil: Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan
      sug:
        subj:
          Urease Antagonists and Inhibitors
          Enzyme Inhibitors
          Carboxylic Acids
          Amides
          Amines
          Chemistry, Analytical
          Descriptive Statistics
          Molecular Structure
          Benzene Derivatives
          Organic Chemicals
          Molecular Docking Simulation
          Spectrophotometry, Infrared
          Magnetic Resonance Spectroscopy
          Mass Spectrometry
      ab: A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl-substituted anilines 1a–b reacted with chloroacetyl chloride to afford intermediates 2a-b, which were then reacted with different halo-substituted benzoic acids 3a–f to prepare the title compounds 4a-l. The chemical structures of final products 4a-l were ascertained by FTIR, 1H NMR, 13C NMR, and mass spectra. The compound 4b showed remarkable activity with IC50 1.6 ± 0.2 nM, better than the standard thiourea having IC50 472.1 ± 135.1 nM. The 2-chloro-substituted phenyl ring on one side of compound 4b and 4-isopropyl-substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver–Burk plots (kinetics study) indicated about 4b derivative as a mixed type of inhibitor. The virtual screening performed against urease enzyme (PDBID 4H9M) showed that compounds 4b and 4e have binding energies of −7.8 and −7.9 Kcal/mol, respectively. Based upon our results, it was found that derivative 4b is a highly potent urease inhibitor, better than the standard thiourea.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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