We synthesized and validated five Schiff base Pt(II) complexes derived from 2-hydroxy-1-naphthaldehyde benzoyl hydrazone and its derivatives, which are modified at the benzohydrazide structures (L1–L5). The complexes were [Pt(L1)(DMSO)Cl] (C1), [Pt(L2)(DMSO)Cl] (C2), [Pt(L3)(DMSO)Cl] (C3), [Pt(L4)(DMSO)Cl] (C4), and [Pt(L5)(DMSO)Cl] (C5). Crystal structures showed that the Pt centers of all complexes were tetra-coordinated with other atoms. The structure-activity relationships and anticancer mechanisms of the complexes were explored. These five Pt(II) complexes were toxic at micromolar doses and exhibited cytotoxicity similar to or somewhat higher than that of cisplatin, with IC₅₀ values ranging from 4.38 μM to 25.16 μM. The complexes exerted chemotherapeutic effects via inhibition of telomerase by targeting the c-myc promoter and down-regulating the expression of human telomerase reverse transcriptase, consequently triggering cell apoptosis. In addition, Pt(II) complexes also caused cell cycle arrest at S-phase, leading to the down-regulation of cdc25 A, cyclin A2, and CDK2 and up-regulation of p53, p27, and p21 proteins. Other complex-associated events were reactive oxygen species production, transformation of the mitochondrial membrane potential (Δψ_m), release of cytochrome c, regulation of Bcl-2 family protein expression, facilitated release of apoptotic active substances, and activation of caspases to induce apoptosis.

我们合成并验证了5种衍生自2-羟基-1-萘醛苯甲酰及其衍生物的席夫碱Pt（II）配合物，这些配合物在苯并酰肼结构上被修饰（L1-L5）。络合物为[Pt（L1）（DMSO）Cl]（C1），[Pt（L2）（DMSO）Cl]（C2），[Pt（L3）（DMSO）Cl]（C3），[Pt（L4） （DMSO）Cl]（C4）和[Pt（L5）（DMSO）Cl]（C5）。晶体结构表明，所有配合物的Pt中心都与其他原子四配位。探索了复合物的构效关系和抗癌机理。这五种Pt（II）复合物在微摩尔剂量下均具有毒性，并显示出与IC ₅₀相似或略高于顺铂的细胞毒性。值范围从4.38μM到25.16μM。该复合物通过靶向c-myc启动子并下调人端粒酶逆转录酶的表达来抑制端粒酶发挥化学治疗作用，从而触发细胞凋亡。此外，Pt（II）复合物还导致细胞周期停滞在S期，导致cdc25 A，cyclin A2和CDK2的下调以及p53，p27和p21蛋白的上调。其他复合物相关事件是活性氧的产生，线粒体膜电位（Δψ转化_米），细胞色素的释放Ç，Bcl-2家族蛋白表达的调节，凋亡的活性物质容易剥离，和胱天蛋白酶诱导细胞凋亡的激活。