Synthesis, molecular structure and urease inhibitory activity of novel -Schiff bases of benzyl phenyl ketone: A combined theoretical and experimental approach.

BACKGROUND

Urease belongs to the family of amid hydrolases with two nickel atoms in their core structure. On the basis of literature survey, this research work is mainly focused on the study of -Schiff base derivatives of benzyl phenyl ketone nucleus.

OBJECTIVE

Synthesis of benzyl phenyl ketone based -Schiff bases in search of potent urease inhibitors.

METHOD

In the current work, -Schiff bases were synthesized through two steps reaction by reacting benzyl phenyl ketone with excess of hydrazine hydrate in ethanol solvent in the first step to get the desired hydrazone. In last, different substituted aromatic aldehydes were refluxed in catalytic amount of acetic acid with the desired hydrazone to obtain -Schiff base derivatives in tremendous yields. Using various spectroscopic techniques including FTIR, HR-ESI-MS, and H NMR spectroscopy were used to clarify the structures of the created -Schiff base derivatives.

RESULTS

The prepared compounds were finally screened for their urease inhibition activity. All the synthesized derivatives (-) showed excellent to less inhibitory activity when compared with standard thiourea (IC = 21.15 ± 0.32 µM). Compounds (IC = 22.21 ± 0.42 µM), (IC = 26.11 ± 0.22 µM) and (IC = 28.11 ± 0.22 µM) were found the most active urease inhibitors near to standard thiourea among the synthesized series. Similarly, compound having IC value of 34.32 ± 0.65 µM showed significant inhibitory activity against urease enzyme. Furthermore, three compounds and exhibited less activity with IC values of 45.91 ± 0.14, 47.91 ± 0.14, and 48.33 ± 0.72 µM respectively. DFT used to calculate frontier molecular orbitals including; HOMO and LUMO to indicate the charge transfer from molecule to biological transfer, and MEP map to indicate the chemically reactive zone suitable for drug action. The electron localization function (ELF), non-bonding orbitals, AIM charges are also calculated. The docking study contributed to the analysis of urease protein binding.