Division of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens, Greece.
Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 157 84 Athens, Greece.
Molecules. 2021 Dec 21;27(1):7. doi: 10.3390/molecules27010007.
The aqueous dissolution profile of the isomeric synthetic adamantane phenylalkylamine hydrochlorides and was probed. These adducts have shown significant antiproliferative/anticancer activity associated with an analgesic profile against neuropathic pain. They are both devoid of toxic effects and show appreciable enzymatic human plasma stability. The structures of these two compounds have been elucidated using 2D NMR experiments, which were used to study their predominant conformations. Compound 's scaffold appeared more flexible, as shown by the NOE spatial interactions between the alkyl bridge chain, the aromatic rings, and the adamantane nucleus. Conversely, compound appeared very rigid, as it did not share significant NOEs between the aforementioned structural segments. MD simulations confirmed the NOE results. The aqueous dissolution profile of both molecules fits well with their minimum energy conformers' features, which stem from the NOE data; this was nicely demonstrated, especially in the case of compound .
对异构体合成金刚烷芳基烷基胺盐酸盐 和 的水溶解析度进行了探究。这些加合物表现出显著的抗增殖/抗癌活性，并具有针对神经病理性疼痛的镇痛特性。它们均没有毒性作用，并表现出可观的人血浆酶稳定性。使用二维 NMR 实验阐明了这两种化合物的结构，这些实验被用于研究它们的主要构象。化合物 的支架似乎更具灵活性，这表现在烷基桥链、芳环和金刚烷核之间的 NOE 空间相互作用上。相反，化合物 表现出非常刚性，因为它在上述结构片段之间没有共享显著的 NOE。MD 模拟证实了 NOE 结果。这两种分子的水溶解析度与它们的最低能量构象特征吻合良好，这源于 NOE 数据；这在化合物 的情况下得到了很好的证明。
