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

Abstract

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.

Synthesis, Kinetics and Computational Explorations of 4‐Phenylpiperazine Bearing N‐(Aryl)‐3‐substituted‐benzamides as Auspicious Tyrosinase Inhibitors

“…The His85 is a core residue existed at the central atom of target protein and is metal bound amino acid paly a significance in protein stability [37] . Our docking results showed good correlation with published research which strengthens our work and efficacy [38–39] . The 2D conformations and binding pose and interactions with binding residues of all the candidate molecules are mentioned in supplementary data (Figures S18–25).…”

“…[37] Our docking results showed good correlation with published research which strengthens our work and efficacy. [38][39] The 2D conformations and binding pose and interactions with binding residues of all the candidate molecules are mentioned in supplementary data (Figures S18-25).…”

Zinc Oxide Nanoparticles Promise Anticancer and Antibacterial Activity in Ovarian Cancer

“…As a beta-lactam antibiotic, it inhibits the third and last stage of bacterial cell wall synthesis. It acts on both gram + ve and gram -ve bacteria [ 57 ]. About 73.6% of E.coli isolates from different clinical specimens in children in 2009 were sensitive to cefaclor [ 58 ].…”

“…Cefadroxil, a first-generation cephalosporin, also works similarly to penicillins. It is more effective for gram + ve [ 57 ]. S. aureus and E.coli attributed in our work were resistant to cefadroxil.…”