Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; The Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain.
Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; Departamento de Química Orgánica and Química Inorgánica, Ctra. Madrid-Barcelona, Km. 33.6, 28871, Universidad de Alcalá, Madrid, Spain.
Bioorg Chem. 2019 May;86:445-451. doi: 10.1016/j.bioorg.2019.01.071. Epub 2019 Feb 1.
In this work six PBN-related indanonitrones 1-6 have been designed, synthesized, and their neuroprotection capacity tested in vitro, under OGD conditions, in SH-SY5Y human neuroblastoma cell cultures. As a result, we have identified indanonitrones 1, 3 and 4 (EC = 6.64 ± 0.28 μM) as the most neuroprotective agents, and in particular, among them, indanonitrone 4 was also the most potent and balanced nitrone, showing antioxidant activity in three experiments [LOX (100 μM), APPH (51%), DPPH (36.5%)], being clearly more potent antioxidant agent than nitrone PBN. Consequently, we have identified (Z)-5-hydroxy-N-methyl-2,3-dihydro-1H-inden-1-imine oxide (4) as a hit-molecule for further investigation.
在这项工作中，设计、合成了六种与 PBN 相关的茚诺酮亚硝酮 1-6，并在缺氧/复氧条件下，在 SH-SY5Y 人神经母细胞瘤细胞培养物中测试了它们的神经保护能力。结果表明，茚诺酮亚硝酮 1、3 和 4（EC=6.64±0.28μM）具有最强的神经保护作用，特别是其中的茚诺酮亚硝酮 4 也是最强和平衡的亚硝酮，在三个实验中显示出抗氧化活性[LOX（100μM）、APPH（51%）、DPPH（36.5%）]，明显比亚硝酮 PBN 更有效力的抗氧化剂。因此，我们将（Z）-5-羟基-N-甲基-2,3-二氢-1H-茚-1-亚胺氧化物（4）确定为进一步研究的命中分子。
