Metal-based drugs have been used in the clinical treatment of tumors for over 30 years. However, no metal-based drugs have been clinically approved to treat glioma. Although metal complexes have excellent cytotoxicity, their most critical problem is crossing the blood–brain barrier. Therefore, to enable metal complexes to cross blood–brain barrier and target glioma therapy, herein, we propose to rationally used the basic structure of diazepam (5-chlorobenzophenone) and thiosemicarbazide to synthesize gold (Au) complexes C1, C2 and C3 with antiglioma activity. The C3 complex with two methyl groups attached to the N3 of thiosemicarbazone exhibited excellent cytotoxicity to glioma cells through its multiaction mechanism against glioma, inducing apoptosis, autophagy death, and deoxyribonucleic acid damage. In addition, the synthesized C3 complex can effectively cross the blood–brain barrier and accumulate in glioma, considerably decreasing the untoward reaction in vivo. Our findings provide a novel strategy for designing metal-based complexes for the treatment of glioma.

中文翻译：

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基于地西泮结构设计新型 Au（III） 复合物：实现针对神经胶质瘤的多作用机制


金属基药物在肿瘤的临床治疗中已有 30 多年的历史。然而，临床上尚未批准使用金属基药物治疗神经胶质瘤。尽管金属络合物具有出色的细胞毒性，但它们最关键的问题是穿过血脑屏障。因此，为了使金属配合物能够穿过血脑屏障并靶向神经胶质瘤治疗，本文我们建议合理使用地西泮（5-氯二苯甲酮）和硫代氨基脲的基本结构来合成具有抗神经胶质瘤活性的金 （Au） 配合物 C1、C2 和 C3。带有两个甲基基团的 C3 复合物连接到巯代氨基甲酮的 N3 上，通过其对抗神经胶质瘤的多重作用机制对神经胶质瘤细胞表现出优异的细胞毒性，诱导细胞凋亡、自噬死亡和脱氧核糖核酸损伤。此外，合成的 C3 复合物可以有效地穿过血脑屏障并在神经胶质瘤中积累，大大减少体内的不良反应。我们的研究结果为设计用于治疗神经胶质瘤的金属基复合物提供了一种新策略。