Department of Chemistry, University of Gujrat, Gujrat, Pakistan.
Department of Chemistry, Govt. College Women University, Sialkot, Pakistan.
J Biomol Struct Dyn. 2024 Jan-Feb;42(1):244-260. doi: 10.1080/07391102.2023.2198609. Epub 2023 Apr 25.
In the present study, a series of 2-amino-4,6-diarylpyrimidine derivatives was designed, synthesized, characterized and evaluated for their α-glucosidase and α-amylase enzyme inhibition assays. The outcomes proved that this class of compounds exhibit considerable inhibitory activity against both enzymes. Among the target compounds, compounds and demonstrated the most potent dual inhibition with IC = 0.087 ± 0.01 μM for α-glucosidase; 0.189 ± 0.02 μM for α-amylase and IC = 0.095 ± 0.03 μM for α-glucosidase; 0.214 ± 0.03 μM for α-amylase, respectively as compared to the standard rutin (IC = 0.192 ± 0.02 μM for α-glucosidase and 0.224 ± 0.02 μM for α-amylase). Remarkably, the enzyme inhibition results indicate that test compounds have stronger inhibitory effect on the target enzymes than the positive control, with a significantly lower IC value. Moreover, these series of compounds were found to inhibit α-glucosidase activity in a reversible mixed-type manner with IC between 0.087 ± 0.01 μM to 1.952 ± 0.26 μM. Furthermore, molecular docking studies were performed to affirm the binding interactions of this scaffold to the active sites of α-glucosidase and α-amylase enzymes. The quantitative structure-activity relationship (QSAR) investigations showed a strong association between structures and their inhibitory actions (IC) with a correlation value () of 0.999916. Finally, molecular dynamic (MD) simulations were carried out to assess the dynamic behavior, stability of the protein-ligand complex, and binding affinity of the most active inhibitor . The experimental and theoretical results therefore exposed a very good compatibility. Additionally, the drug-likeness assay revealed that some compounds exhibit a linear association with Lipinski's rule of five, indicating good drug-likeness and bioactivity scores for pharmacological targets.Communicated by Ramaswamy H. Sarma.
在本研究中，设计、合成、表征了一系列 2-氨基-4,6-二芳基嘧啶衍生物，并对其α-葡萄糖苷酶和α-淀粉酶抑制活性进行了评价。结果表明，这一类化合物对两种酶均表现出相当强的抑制活性。在目标化合物中，化合物 和 对α-葡萄糖苷酶的抑制活性最强，IC = 0.087 ± 0.01 μM；对α-淀粉酶的抑制活性为 0.189 ± 0.02 μM，IC = 0.095 ± 0.03 μM；对α-葡萄糖苷酶的抑制活性为 0.214 ± 0.03 μM，与标准芦丁（IC = 0.192 ± 0.02 μM 对α-葡萄糖苷酶和 0.224 ± 0.02 μM 对α-淀粉酶）相比。值得注意的是，酶抑制结果表明，测试化合物对靶酶的抑制作用强于阳性对照，IC 值显著降低。此外，发现该系列化合物以可逆混合抑制方式抑制α-葡萄糖苷酶活性，IC 值在 0.087 ± 0.01 μM 至 1.952 ± 0.26 μM 之间。此外，还进行了分子对接研究，以确认该支架与α-葡萄糖苷酶和α-淀粉酶酶的活性部位的结合相互作用。定量构效关系（QSAR）研究表明，结构与抑制作用（IC）之间存在很强的相关性（r 值）为 0.999916。最后，进行了分子动力学（MD）模拟，以评估最活跃抑制剂 的配体复合物的动态行为、稳定性和结合亲和力。实验和理论结果因此表现出很好的兼容性。此外，药物相似性测定表明，一些化合物与利宾斯基五规则呈线性关系，表明对药理学靶标具有良好的药物相似性和生物活性评分。由拉玛斯瓦米·H·萨尔马传达。
