The Blue Chemistry Lab, Department of Pharmacy, University of Naples Federico II, 80138 Napoli, Italy.
Laboratoire Molécules de Communication et Adaptation des Micro-organismes, UMR 7245 CNRS, Muséum National d'Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France.
Mar Drugs. 2019 Aug 15;17(8):472. doi: 10.3390/md17080472.
Thirteen nitrogen-containing molecules (/ and -) were isolated from the Indonesian sponge , highlighting the richness of this organism as a source of alkaloids. Their structures were elucidated using one- and two-dimensional NMR spectroscopy and HR-ESI-MS, while the stereochemistry of the diketopiperazines was established using Marfey's method. All compounds were screened in our standard bioactivity assays, including antibacterial, antikinases, and amyloid β-42 assays. The most interesting bioactivity result was obtained with the known acanthocyclamine A (), which revealed for the first time a specific antimicrobial activity and an inhibitory effect on amyloid β-42 production induced by aftin-5 and no cytotoxicity at the dose of 26 µM. These results highlight the potentiality of a bipiperidine scaffold as a promising skeleton for preventing or reducing the production of amyloid β-42, a key player in the initiation of Alzheimer's disease.
从印度尼西亚海绵中分离得到了 13 种含氮分子(/ 和 -),这突出了这种生物作为生物碱来源的丰富性。使用一维和二维 NMR 光谱和 HR-ESI-MS 阐明了它们的结构,而二酮哌嗪的立体化学则使用 Marfey 法确定。所有化合物均在我们的标准生物活性测定中进行了筛选,包括抗菌、抗激酶和淀粉样蛋白β-42 测定。最有趣的生物活性结果来自已知的 acanthocyclamine A (),它首次显示出对 aftin-5 诱导的淀粉样蛋白β-42 产生的特异性抗菌活性和抑制作用,并且在 26 µM 剂量下没有细胞毒性。这些结果突出了双哌啶骨架作为预防或减少淀粉样蛋白β-42 产生的有前途的骨架的潜力,淀粉样蛋白β-42 是阿尔茨海默病发病的关键因素。