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Metal centers and aromatic moieties in Schiff base complexes: impact on G-quadruplex stabilization and oncogene downregulation
Inorganic Chemistry Frontiers ( IF 6.1 ) Pub Date : 2024-07-18 , DOI: 10.1039/d4qi01394h Aurane Froux 1, 2 , Luisa D'Anna 1 , Aurianne Rainot 1, 3 , Camille Neybecker 2 , Angelo Spinello 1 , Riccardo Bonsignore 1 , Raphaël Rouget 2 , Guillaume Harlé 2 , Alessio Terenzi 1 , Antonio Monari 3 , Stéphanie Grandemange 2 , Giampaolo Barone 1
Inorganic Chemistry Frontiers ( IF 6.1 ) Pub Date : 2024-07-18 , DOI: 10.1039/d4qi01394h Aurane Froux 1, 2 , Luisa D'Anna 1 , Aurianne Rainot 1, 3 , Camille Neybecker 2 , Angelo Spinello 1 , Riccardo Bonsignore 1 , Raphaël Rouget 2 , Guillaume Harlé 2 , Alessio Terenzi 1 , Antonio Monari 3 , Stéphanie Grandemange 2 , Giampaolo Barone 1
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We present the synthesis and characterization of novel square planar transition metal complexes of Schiff base ligands, which act as guanine quadruplex binders and stabilizers. The complexes stabilize quadruplexes related to telomere stability or present in oncogene regulatory sequences, as determined by optical spectroscopy, pointing out the emergence of selectivity towards specific structures or sequences. These results are supported and rationalized by molecular modeling simulations. Furthermore, we show that the treatment of cancer cell lines with our complexes is associated with the increase in the number of nuclear guanine quadruplexes and the downregulation in the expression of the considered oncogenes. Remarkably, only very moderate cytotoxicity can be observed for all complexes. These results pave the way for the development of selective anticancer treatment by metal compounds targeting the expression of specific oncogenes.
中文翻译：
席夫碱配合物中的金属中心和芳香族部分：对 G-四链体稳定性和癌基因下调的影响
我们介绍了席夫碱配体的新型方形平面过渡金属配合物的合成和表征，该配合物充当鸟嘌呤四联体粘合剂和稳定剂。通过光谱测定，这些复合物稳定了与端粒稳定性相关或存在于癌基因调控序列中的四链体，指出了对特定结构或序列的选择性的出现。这些结果得到分子建模模拟的支持和合理化。此外，我们表明，用我们的复合物治疗癌细胞系与核鸟嘌呤四链体数量的增加和所考虑的癌基因表达的下调有关。值得注意的是，所有复合物仅观察到非常中等的细胞毒性。这些结果为通过靶向特定癌基因表达的金属化合物开发选择性抗癌治疗铺平了道路。
更新日期：2024-07-18
中文翻译：
席夫碱配合物中的金属中心和芳香族部分：对 G-四链体稳定性和癌基因下调的影响
我们介绍了席夫碱配体的新型方形平面过渡金属配合物的合成和表征，该配合物充当鸟嘌呤四联体粘合剂和稳定剂。通过光谱测定，这些复合物稳定了与端粒稳定性相关或存在于癌基因调控序列中的四链体，指出了对特定结构或序列的选择性的出现。这些结果得到分子建模模拟的支持和合理化。此外，我们表明，用我们的复合物治疗癌细胞系与核鸟嘌呤四链体数量的增加和所考虑的癌基因表达的下调有关。值得注意的是，所有复合物仅观察到非常中等的细胞毒性。这些结果为通过靶向特定癌基因表达的金属化合物开发选择性抗癌治疗铺平了道路。
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