Generation, optimization and characterization of novel anti-prion compounds
Generation, optimization and characterization of novel anti-prion compounds
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DOI：
10.1016/j.bmc.2020.115717
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发表时间：
2020-11-01
影响因子：
3.5
通讯作者：
Kurkin, Alexander, V
中科院分区：
文献类型：
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作者：
Altieri, Andrea;Spiridonov, Evgeny A.;Kurkin, Alexander, V
Prion是一种错误折叠的蛋白质，与兽医和公共卫生高度关注的神经退行性疾病有关。在这项工作中，我们报道了围绕反病毒化合物BB 0300674的化学空间探索，以了解其构效关系(SARS)。基于四个不同的化学簇合成了一系列43个新的类似物，并对PrPSc和突变的PrP进行了毒性测试。通过这一生物筛选，出现了两个化合物(59和65)，与最初的先导化合物相比，其抗蛋白活性提高了10倍，同时呈现出令人感兴趣的细胞活力。
Prions are misfolded proteins involved in neurodegenerative diseases of high interest in veterinary and public health. In this work, we report the chemical space exploration around the anti-prion compound BB 0300674 in order to gain an understanding of its Structure Activity Relationships (SARs). A series of 43 novel analogues, based on four different chemical clusters, were synthetized and tested against PrPSc and mutant PrP toxicity assays. From this biological screening, two compounds (59 and 65) emerged with a 10-fold improvement in anti-prion activity compared with the initial lead compound, presenting at the same time interesting cell viability.