Synthesis and biological evaluation of 2-nitrocinnamaldehyde derived thiosemicarbazones as urease inhibitors

Abstract

Hyperactivity of urease enzyme induces pathogenesis of peptic ulcers and gastritis. The excess of urease can be reduced by introducing various inhibitors. The risk of high urease content also partakes in agriculture field where it declines the environmental health. This alarming situation leads to the mandatory quest of such novel scaffolds that must work wonders in the field of medicinal chemistry. Consequently, we herein report a novel series of N4-substitution of cinnamaldehyde with thiosemicarbazones 3a-q as potential candidates for urease inhibition. These new N4-substituted thiosemicarbazones 3a-q of indistinct chemical scaffolds were characterized by advanced spectroscopic techniques, such as ESI-MS, 13CNMR, 1HNMR, and FTIR. All newly synthesized compounds showed significant urease inhibitions with IC50 values in range of 11.4 ± 0.23 to 80.6 ± 0.52 μM. Furthermore, kinetic studies of compound 3o displayed competitive type of inhibition with ki value 8.65 ± 0.37 µM. For analysis of structure‒activity relationship and interactions pattern of all compounds, molecular docking was used, which revealed excellent binding interactions of compounds with the active site residues, such as nickel atom coordination, π–cation, π–π interactions, and hydrogen bonding. Additionally, the predicted pharmacokinetics and drug-likeness of compounds suggest that these compounds have good pharmacokinetic and physicochemical properties, and these compounds follow rules of drug-likeness.