Cephalosporin as Potent Urease and Tyrosinase Inhibitor: Exploration through Enzyme Inhibition, Kinetic Mechanism, and Molecular Docking Studies.

In present study, eleven cephalosporin drugs were selected to explore their new medically important enzyme targets with inherited safety advantage. To this end, selected drugs with active ingredient, cefpodoxime proxetil, ceftazidime, cefepime, ceftriaxone sodium, cefaclor, cefotaxime sodium, cefixi...

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Publicado en:BioMed Research International pp. 1 - 12
Autores principales: Alqahtani, Yahya S., Alyami, Bandar A., Alqarni, Ali O., Mahnashi, Mater H., Ali, Anser, Javed, Qamar, Hassan, Mubashir, Ehsan, Muhammad
Formato: research tables/charts Journal Article
Publicado: Wiley-Blackwell 7/28/2022
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 7/28/2022
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      pub: Wiley-Blackwell
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        10.1155/2022/1092761
        158239225
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        atl: Cephalosporin as Potent Urease and Tyrosinase Inhibitor: Exploration through Enzyme Inhibition, Kinetic Mechanism, and Molecular Docking Studies.
      aug:
        au:
          Alqahtani, Yahya S.
          Alyami, Bandar A.
          Alqarni, Ali O.
          Mahnashi, Mater H.
          Ali, Anser
          Javed, Qamar
          Hassan, Mubashir
          Ehsan, Muhammad
        affil: Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Saudi Arabia
      sug:
        subj:
          Cephalosporins Therapeutic Use
          Urease Therapeutic Use
          Enzyme Inhibitors Therapeutic Use
          Molecular Docking Simulation
          Safety
          Human
          Cefaclor
          Cefotaxime
          Cefepime Hydrochloride
          Antibiotics
          Oxidoreductases
          Phenols
          Kinetics
          Ceftriaxone
          Enzymes
          In Vitro Studies
      ab: In present study, eleven cephalosporin drugs were selected to explore their new medically important enzyme targets with inherited safety advantage. To this end, selected drugs with active ingredient, cefpodoxime proxetil, ceftazidime, cefepime, ceftriaxone sodium, cefaclor, cefotaxime sodium, cefixime trihydrate, cephalexin, cefadroxil, cephradine, and cefuroxime, were evaluated and found to have significant activity against urease (IC 50 = 0.06 ± 0.004 to 0.37 ± 0.046 mM) and tyrosinase (IC 50 = 0.01 ± 0.0005 to 0.12 ± 0.017 mM) enzymes. Urease activity was lower than standard thiourea; however, tyrosinase activity of all drugs outperforms (ranging 6 to 18 times) the positive control: hydroquinone (IC 50 = 0.18 ± 0.02 mM). Moreover, the kinetic analysis of the most active drugs, ceftriaxone sodium and cefotaxime sodium, revealed that they bind irreversibly with both the enzymes; however, their mode of action was competitive for urease and mixed-type, preferentially competitive for tyrosinase enzyme. Like in vitro activity, ceftriaxone sodium and cefotaxime sodium docking analysis showed their considerable binding affinity and significant interactions with both urease and tyrosinase enzymes sufficient for downstream signaling responsible for observed enzyme inhibition in vitro, purposing them as potent candidates to control enzyme-rooted obstructions in future.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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