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.

脲酶的过度活跃诱发消化性溃疡和胃炎的发病机制。可以通过引入各种抑制剂来降低脲酶的过量。高脲酶含量的风险也存在于农业领域，它会降低环境健康。这种令人担忧的情况导致了对这种必须在药物化学领域创造奇迹的新型支架的强制性探索。因此，我们在此报告了一系列新的N ⁴ -用缩氨基硫脲3a-q取代肉桂醛作为脲酶抑制的潜在候选物。这些新的N ⁴取代的缩氨基硫脲3a-q的模糊化学支架通过先进的光谱技术（如 ESI-MS）进行了表征，¹³ CNMR、¹ HNMR 和 FTIR。所有新合成的化合物都显示出显着的脲酶抑制作用，IC ₅₀值在 11.4 ± 0.23 至 80.6 ± 0.52 μM 的范围内。此外，化合物3o的动力学研究显示竞争性抑制，ki 值为 8.65 ± 0.37 µM。为了分析所有化合物的结构-活性关系和相互作用模式，使用分子对接，揭示了化合物与活性位点残基的良好结合相互作用，例如镍原子配位、π-阳离子、π-π相互作用和氢键. 此外，预测的化合物药代动力学和类药性表明这些化合物具有良好的药代动力学和理化性质，并且这些化合物遵循类药性规则。