State Key Laboratory for Modification of Chemicals Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.
Department of Chemistry, GC University Faisalabad, Sub campus Layyah 31200, Pakistan.
Molecules. 2019 Jan 16;24(2):312. doi: 10.3390/molecules24020312.
The present study focuses on the design and synthesis of a cage-like organic skeleton containing two triazole rings jointed via imine linkage. These molecules can act as urease inhibitors. The in-vitro urease inhibition screening results showed that the combination of the two triazole skeleton in the cage-like morphology exhibited comparable urease inhibition activity to that of the reference thiourea while the metallic complexation, especially with copper, nickel, and palladium, showed excellent activity results with IC values of 0.94 ± 0.13, 3.71 ± 0.61, and 7.64 ± 1.21 (⁻), and 1.20 ± 0.52, 3.93 ± 0.45, and 12.87 ± 2.11 µM (⁻). However, the rest of compounds among the targeted series exhibited a low to moderate enzyme inhibition potential. To better understand the compounds' underlying mechanisms of the inhibitory effect ( and ) and their most active metal complexes ( and ), we performed an enzymatic kinetic analysis using the Lineweaver⁻Burk plot in the presence of different concentrations of inhibitors to represent the non-competitive inhibition nature of the compounds, , , and , while mixed type inhibition was represented by the compound, . Moreover, molecular docking confirmed the binding interactive behavior of within the active site of the target protein.
本研究专注于设计和合成一种含有两个通过亚胺键连接的三唑环的笼状有机骨架。这些分子可以作为脲酶抑制剂。体外脲酶抑制筛选结果表明，笼状形态中两个三唑骨架的组合表现出与参考硫脲相当的脲酶抑制活性，而金属络合，特别是与铜、镍和钯的络合，表现出优异的活性，IC 值分别为 0.94 ± 0.13、3.71 ± 0.61 和 7.64 ± 1.21（⁻），以及 1.20 ± 0.52、3.93 ± 0.45 和 12.87 ± 2.11 µM（⁻）。然而，目标系列中的其余化合物表现出低至中等的酶抑制潜力。为了更好地理解化合物抑制作用的潜在机制（和）及其最活跃的金属配合物（和），我们在存在不同浓度抑制剂的情况下使用 Lineweaver-Burk 图进行了酶动力学分析，以表示化合物、、、和的非竞争性抑制性质，而化合物则代表混合类型抑制。此外，分子对接证实了化合物在靶蛋白活性位点的结合相互作用行为。
