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, cefixime trihydrate, cephalexin, cefadroxil, cephradine, and cefuroxime, were evaluated and found to have significant activity against urease (IC50 = 0.06 +/- 0.004 to 0.37 +/- 0.046mM) and tyrosinase (IC50 = 0.01 +/- 0.0005 to 0.12 +/- 0.017mM) enzymes. Urease activity was lower than standard thiourea; however, tyrosinase activity of all drugs outperforms (ranging 6 to 18 times) the positive control: hydroquinone (IC50 = 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.

Automated summary

In this study, 11 cephalosporin drugs were evaluated for their activity against urease and tyrosinase enzymes. The drugs showed significant activity, with ceftriaxone sodium and cefotaxime sodium being the most active. These drugs bind irreversibly to the enzymes and have the potential to be used as potent candidates for the treatment of enzyme-related diseases.