Solvent-free Mechano-chemical Synthesis of New Omeprazole Derived Metal Complexes: Characterization, Urease Inhibitory Kinetics and Selective Anti-Helicobacter pylori Activity

Background: Metal-based antimicrobial agents have recently been identified as an alternate therapy for the treatment of infectious diseases. This investigation relates to one-pot solvent-free preparation of some new transition metal complexes of omeprazole (OMP), followed by their characterization and in vitro applications as anti-Helicobacter pylori agents and urease inhibitors. Methods: The complexes were characterized by elemental analyzer, IR, Powder X-Ray diffraction, H-1-NMR, C-13-NMR and mass spectrometric and thermal methods, which elucidated that the complexes have the general formula [ML] X where M =Zn, Ni, Cu and X =CH3COO-and [ML] X. H2O, where M -Co, X -CH3COO. The complexes exhibited antibacterial activity against selected strains of Gram +ve and Gram -ve bacteria including Staphylococcus aureus (ATCC 29213), S. epidermidis (ATCC 12228), Escherichia coli (ATCC 12435), Proteus vulgaris (NCTC 4175), Pseudomonas aeruginosa (ATCC 49189) and fifteen local isolates and two reference strains of H. pylori. Zinc omeprazole (Zn-OMP), cobalt omeprazole (Co-OMP) and copper omeprazole (Cu-OMP), all exhibited potent and selective anti-H. pylori activity in the range of 1.0-16 mu gmL(-1), 8.0-64 mu gmL(-1)and 32-128 mu gmL(-1), respectively. Results: However, all of the complexes showed mild anti-bacterial activity against rest of the tested strains. Amoxicillin (break points of 1 <=) was used as a reference standard. Zn-OMP was found to be equally effective against the antibiotic-resistant and antibiotic-susceptible strains of H. pylori, whereas Co-OMP and Cu-OMP exhibited mixed trends. Urease inhibition was evaluated by using the urease isolated from H. pylori reference. Zn-OMP was found to be the most potent urease inhibitor followed by Cu-OMP and then Co-OMP. Lineweaver-Burk plots were used to determine Michaelis Menten constant for elucidating the mechanism of inhibition. Conclusion: The results of the present work revealed that the devised mechano-chemical method can be explored as an environment-friendly route for the synthesis of metal based anti-H. plyori drugs.