Synthetic Transformation of 2-{2-Fluoro[1,1′-biphenyl]-4-yl} Propanoic Acid into Hydrazide–Hydrazone Derivatives: <i>In Vitro</i> Urease Inhibition and <i>In Silico</i> Study

Abstract

In the present study, 28 acyl hydrazones (<b>4-31</b>) of flurbiprofen were synthesized in good to excellent yield by reacting different aromatic aldehydes with the commercially available drug flurbiprofen. The compounds were deduced with the help of different spectroscopic techniques like ¹H-NMR and HREI-MS and finally evaluated for <i>in vitro</i> urease inhibitory activity. All of the synthesized products demonstrated good inhibitory activities in the range of IC₅₀ = 18.92 ± 0.61 to 90.75 ± 7.71 μM as compared to standard thiourea (IC₅₀ = 21.14 ± 0.42 μM). Compound <b>30</b> was found to be the most active among the series better than the standard thiourea. A structure-activity relationship (SAR) study revealed that the presence of electron-donating groups on the phenyl ring plays a prominent role in the inhibition of the urease enzyme. Moreover, <i>in silico</i> molecular modeling analysis was carried out to study the effect of substituents in synthesized derivatives on the binding interactions with the urease enzyme.