Levofloxacin and sulfa drugs linked via Schiff bases: Exploring their urease inhibition, enzyme kinetics and in silico studies

Involvement of urease in various pathological conditions specifically in gastric and peptic ulcers make it an important therapeutic target. In the present study urease inhibition was investigated by newly designed Schiff bases of levofloxacin. Structure elucidation of these compounds were done by spectral studies such as IR, H-1 NMR and C-13 NMR and elemental analysis. In vitro urease enzyme inhibition assay revealed the compounds LS01, LS06 and LS07 were found to be the most potent and showed comparable IC50 values 0.58 +/- 0.11, 0.45 +/- 0.21 mu M and 0.52 +/- 0.28 mu M respectively. The compound LS06 was competitive inhibitor with Ki value 1.13 mu M while the compounds LS01 and LS07 were mixed type of inhibitors with Ki values 3.40 and 6.03 mu M respectively. Plausible binding mode of competitive inhibitor was predicted using molecular docking studies. Ancillary to synthetic studies, density functional theory (DFT) at B3LYP/6-31G(d,p) basis sets in ground state is utilized in order to gain optimized geometries of LS01-LS09 molecules. Different geometric parameters like molecular electrostatic potential analysis, alignment of HOMO and LUMO levels, natural bonding orbital (NBO) analysis and global descriptor of reactivity were performed in support of experimental findings. All DFT based computed results showed best agreement with experimental finding and suggest that all synthesized compounds are chemically stable. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study investigated the inhibition of urease by newly designed Schiff bases of levofloxacin, revealing LS01, LS06, and LS07 as the most potent inhibitors with comparable IC50 values. Molecular docking studies predicted the binding mode of the competitive inhibitor. DFT calculations supported experimental findings and confirmed the chemical stability of all synthesized compounds.