酶是生物大分子，已被认为是重要的药物靶点，其调节紊乱导致各种病理状况，如炎症、寄生虫感染、阿尔茨海默病、癌症等。本研究中，我们设计并合成了一些新型氧杂杨梅环连接的新型橙蓟菊素，评估其作为CTS乙型蛋白酶（CTSB）、α-淀粉酶、脂肪酶的潜在抑制剂，以及对凝血酶的激活剂。所有新合成的化合物均通过各种光谱技术（1H NMR、13C NMR、HRMS）进行了全面的表征，并根据单晶XRD数据和1H NMR化学位移值确定了它们的Z构型。此外，我们评估了这些杂交物的胞内（CTSB）和胞外（凝血酶、脂肪酶、α-淀粉酶）酶抑制活性。体外抑制筛选结果显示，其中大部分合成化合物是良好的竞争性抑制剂（抑制率 = 22.91-75.04），其中6q（抑制率=75.04）和6r（抑制率=71.13）是该系列的杰出抑制剂。同时，它们对α-淀粉酶（抑制率 = 7.22-22.48）和脂肪酶（抑制率 = 16.29-54.83）表现出弱至中等的抑制作用。即使在微摩尔浓度下，这些化合物仍显示出显著的凝血酶激活作用（激活率 = 107.42-196.47）。此外，药物建模研究显示，在所有测试的酶中，体外实验结果与筛选化合物的计算结合亲和力之间存在良好的相关性。这些发现有望为涉及这些酶的不同病理疾病的药物开发提供新的线索。版权所有 © 2023 Elsevier Inc. 保留所有权利。

Enzymes are the biological macromolecules that have emerged as an important drug target as their upregulation/imbalance leads to various pathological conditions, such as inflammation, parasitic infection, Alzheimer's, cancer, and many others. Here, we designed and synthesized some morpholine tethered novel aurones and evaluated them as potential inhibitors for CTSB, α-amylase, lipase and activator for trypsin. All the newly synthesized compounds were fully characterized by various spectroscopic techniques (1H NMR, 13C NMR, HRMS) and the Z-configuration to them was assigned based on single crystal XRD data and 1H NMR chemical shift values. Further, the hybrids were evaluated for their intracellular (cathepsin B) and extracellular (trypsin, lipase, amylase) enzyme inhibition potencies. The in-vitro inhibition screening against cathepsin B revealed that most of the synthesized compounds are good competitive inhibitors (% inhibition = 22.91-75.04), with 6q (% inhibition = 75.04) and 6r (% inhibition = 71.13) as the eminent inhibitors of the series. At the same time, they exhibited weak to moderate inhibition towards amylase (% inhibition = 7.22-22.48) and lipase (% inhibition = 16.29-54.83). A significant trypsin activation (% activation = 107.42-196.47) was observed even at the micromolar concentration of the compounds. Furthermore, the drug-modeling studies showed a good correlation between the in-vitro experimental results and the calculated binding affinity of the screened compounds with all the tested enzymes. These findings are expected to provide a new lead in drug development for different pathological disorders wherever these enzymes are involved.Copyright © 2023 Elsevier Inc. All rights reserved.