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Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines†
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2018-04-17 00:00:00 , DOI: 10.1039/c8md00095f Itamar Luís Gonçalves 1 , Liliana Rockenbach 1 , Gustavo Machado das Neves 1 , Gabriela Göethel 2 , Fabiana Nascimento 1 , Luciano Porto Kagami 1 , Fabrício Figueiró 3 , Gabriel Oliveira de Azambuja 1 , Amanda de Fraga Dias 3 , Andressa Amaro 3 , Lauro Mera de Souza 4 , Ivan da Rocha Pitta 5 , Daiana Silva Avila 6 , Daniel Fábio Kawano 7 , Solange Cristina Garcia 2 , Ana Maria Oliveira Battastini 3 , Vera Lucia Eifler-Lima 1
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2018-04-17 00:00:00 , DOI: 10.1039/c8md00095f Itamar Luís Gonçalves 1 , Liliana Rockenbach 1 , Gustavo Machado das Neves 1 , Gabriela Göethel 2 , Fabiana Nascimento 1 , Luciano Porto Kagami 1 , Fabrício Figueiró 3 , Gabriel Oliveira de Azambuja 1 , Amanda de Fraga Dias 3 , Andressa Amaro 3 , Lauro Mera de Souza 4 , Ivan da Rocha Pitta 5 , Daiana Silva Avila 6 , Daniel Fábio Kawano 7 , Solange Cristina Garcia 2 , Ana Maria Oliveira Battastini 3 , Vera Lucia Eifler-Lima 1
Affiliation
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An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called 20h and 20e, with an anti-proliferative effects, achieving IC50 values of about half that of the IC50 of monastrol in both cell lines. As with monastrol, flow cytometry analyses showed that the 20e and 20h compounds induced cell cycle arrest in the G2/M phase, and immunocytochemistry essays revealed the formation of monopolar spindles due to Eg5 inhibition without any toxicity to Caenorhabditis elegans.
中文翻译：
monastrol N-1 芳基化对神经胶质瘤细胞系中驱动蛋白 Eg5 抑制的影响†
为了发现比模板更有效的 Eg5 配体，设计并合成了由 monastrol 衍生的 N-1 芳基取代的两组二氢嘧啶-2-硫酮 (DHPM) 的原始且集中的库。基于分子对接研究，选择四种配体对两种神经胶质瘤细胞系进行药理学研究。结果发现了两种具有抗增殖作用的原始化合物，称为20h和20e ，在两种细胞系中实现的 IC 50值约为 monastrol IC 50的一半。与 monastrol 一样，流式细胞术分析表明20e和20h化合物诱导细胞周期停滞在 G 2 /M 期，免疫细胞化学论文揭示了由于 Eg5 抑制而形成单极纺锤体，而对秀丽隐杆线虫没有任何毒性。
更新日期：2018-04-17
中文翻译：
monastrol N-1 芳基化对神经胶质瘤细胞系中驱动蛋白 Eg5 抑制的影响†
为了发现比模板更有效的 Eg5 配体，设计并合成了由 monastrol 衍生的 N-1 芳基取代的两组二氢嘧啶-2-硫酮 (DHPM) 的原始且集中的库。基于分子对接研究，选择四种配体对两种神经胶质瘤细胞系进行药理学研究。结果发现了两种具有抗增殖作用的原始化合物，称为20h和20e ，在两种细胞系中实现的 IC 50值约为 monastrol IC 50的一半。与 monastrol 一样，流式细胞术分析表明20e和20h化合物诱导细胞周期停滞在 G 2 /M 期，免疫细胞化学论文揭示了由于 Eg5 抑制而形成单极纺锤体，而对秀丽隐杆线虫没有任何毒性。
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