To develop the next-generation metal agents for efficiently inhibiting tumor growth, we synthesized a series of new Zn(II) complexes (C1–C5) derived from 2-pyridinecarboxaldehyde thiosemicarbazone and investigated their structure–activity relationships. C5 bearing two methyl groups at the N-4 position of the ligand exerted the strongest inhibition effect among all the Zn(II) complexes. Importantly, C5 exerted an effective inhibitory effect on tumor growth and produced few side effects in vivo. We further confirmed the antitumor mechanisms of C5, including arresting the cell cycle at the S phase, inducing apoptosis, inducing lethal autophagy, and suppressing angiogenesis.

中文翻译：

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具有显着抗肿瘤和抗血管生成活性的锌 (II) 2-吡啶甲醛缩氨基硫脲复合物的开发

为了开发可有效抑制肿瘤生长的下一代金属试剂，我们合成了一系列衍生自 2-吡啶甲醛缩氨基硫脲的新型 Zn( II ) 配合物 ( C1–C5 )，并研究了它们的构效关系。在配体的N-4位带有两个甲基的C5在所有Zn( II )配合物中发挥了最强的抑制作用。重要的是，C5对肿瘤生长具有有效的抑制作用，并且在体内产生的副作用很少。我们进一步证实了C5的抗肿瘤机制，包括将细胞周期阻滞在 S 期、诱导细胞凋亡、诱导致死性自噬和抑制血管生成。