Mechanochemical synthesis and in vitro anti-Helicobacter pylori and uresase inhibitory activities of novel zinc(II)–famotidine complex

Abstract

The mechanochemical synthesis and characterization of a zinc complex with famotidine is described. The complex was characterized by microanalysis and a number of spectroscopic techniques. The complex was of M:L dihydrate type. Derivatization of famotidine with zinc appears to enhance the activity of the drug by inhibiting the growth of Helicobacter pylori (two reference and 34 clinical isolates). The complex inhibited the growth of H. pylori in an MIC range of 1–8 μg mL⁻¹. The anti-H. pylori activity of the zinc–famotidine complex against antibiotic-resistant strains was nearly comparable to that of antibiotic-susceptible strains. The complex was found to be far less toxic than the parent drug, as demonstrated by its higher LD₅₀ value. In the human urease enzyme inhibition assay the complex exhibited significant inhibition. The new complex appears to be more useful in eradicating both the antibiotic-susceptible and antibiotic-resistant strains of H. pylori.

Keywords::

• Zinc complexes
• zinc–famotidine
• antiulcer drugs
• metal-based drugs
• anti-H. pylori activity
• mechanochemical synthesis
• urease inhibition

Acknowledgments

The authors gratefully acknowledge Dr. J. P. H. Charmant, Dr. C. J. Adams, and M. Lusi of the School of Chemistry, University of Bristol, UK, for their assistance and useful suggestions during this work.

Declaration of interset: There is no conflict of interest associated with this work. One of the authors (M.A.) is grateful to the Higher Education Commission of Pakistan for providing financial assistance to study at the University of Bristol.