Department of Chemistry, South-West University "Neofit Rilski", 2700 Blagoevgrad, Bulgaria.
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Molecules. 2020 Sep 1;25(17):3989. doi: 10.3390/molecules25173989.
A series of nineteen amino acid analogues of amantadine (Amt) and rimantadine (Rim) were synthesized and their antiviral activity was evaluated against influenza virus A (H3N2). Among these analogues, the conjugation of rimantadine with glycine illustrated high antiviral activity combined with low cytotoxicity. Moreover, this compound presented a profoundly high stability after in vitro incubation in human plasma for 24 h. Its thermal stability was established using differential and gravimetric thermal analysis. The crystal structure of glycyl-rimantadine revealed that it crystallizes in the orthorhombic space group. The structure-activity relationship for this class of compounds was established, with CoMFA (Comparative Molecular Field Analysis) 3D-Quantitative Structure Activity Relationships (3D-QSAR) studies predicting the activities of synthetic molecules. In addition, molecular docking studies were conducted, revealing the structural requirements for the activity of the synthetic molecules.
合成了一系列 19 种金刚烷胺（Amt）和瑞米德林（Rim）的氨基酸类似物，并评估了它们对甲型流感病毒（H3N2）的抗病毒活性。在这些类似物中，金刚烷胺与甘氨酸的结合表现出高抗病毒活性和低细胞毒性。此外，该化合物在人血浆中孵育 24 小时后表现出极高的稳定性。使用差示和重量热分析确定了其热稳定性。甘氨酰瑞米德林的晶体结构表明其结晶为正交晶系。建立了这类化合物的构效关系，用比较分子场分析（CoMFA）三维定量构效关系（3D-QSAR）研究预测了合成分子的活性。此外，还进行了分子对接研究，揭示了合成分子活性的结构要求。
