为了寻找潜在的抗癌药物，我们合成了基于 SNO 供体水杨醛亚胺主要配体的 Pt(II) 配合物，在转位 (C1-C6) 上带有 NH3 作为辅助配体。这些配合物在结构上与转铂相似，因为主配体和 NH3 辅助配体的两个 N 供体原子彼此配位至 Pt 反位。通过详细的光谱和分光光度方法对主配体上具有不同取代基的每个配合物进行了彻底的表征。通过单晶 X 射线分析对其中四种复合物进行了固态研究。使用 1H NMR 方法在 DMSO-d6 或其与 D2O 的混合物中的溶液状态下测量参考配合物 C1 的稳定性。进一步研究了这些复合物在三阴性乳腺癌 (TNBC) 细胞（包括 MDA-MB-231、MDA-MB-468 和 MDA-MB-436 细胞）中的抗癌活性。 MTT结果显示，所有这些复合物均显示出令人满意的细胞毒作用。重要的是，将高活性复合物 C4 抗癌效果与标准化疗药物（包括顺铂、奥沙利铂和 5-氟尿嘧啶 (5-FU)）进行了比较。从功能上讲，C4 抑制癌细胞的侵袭、球体形成能力和克隆形成潜力。当C4与palbociclib、JQ1和紫杉醇联合使用时，在TNBC细胞中表现出协同抗癌作用。从机制上讲，C4 抑制细胞周期蛋白依赖性激酶 (CDK)4/6 通路并靶向 MYC/STAT3/CCND1/CNNE1 轴的表达。此外，C4 抑制 EMT 信号通路，这表明 C4 在抑制 TNBC 转移中发挥作用。我们的研究结果可能为这些复合物作为不同类型人类癌症的潜在化疗药物的详细机制研究奠定基础。版权所有 © 2024 Elsevier Inc. 保留所有权利。

In search of potential anticancer agents, we synthesized SNO-donor salicylaldimine main ligand-based Pt(II) complexes bearing NH3 as co-ligand at trans-position (C1-C6). These complexes showed similarity in structure with transplatin as the two N donor atoms of the main ligand and NH3 co-ligand were coordinated to Pt in trans position to each other. Each complex with different substituents on the main ligand was characterized thoroughly by detailed spectroscopic and spectrophotometric methods. Four of these complexes were studied in solid state by single crystal X-ray analysis. The stability of reference complex C1 was measured in solution state in DMSO‑d6 or its mixture with D2O using 1H NMR methods. These complexes were further investigated for their anticancer activity in triple-negative-breast (TNBC) cells including MDA-MB-231, MDA-MB-468 and MDA-MB-436 cells. All these complexes showed satisfactory cytotoxic effect as revealed by the MTT results. Importantly, the highly active complex C4 anticancer effect was compared to the standard chemotherapeutic agents including cisplatin, oxaliplatin and 5-fluorouracil (5-FU). Functionally, C4 suppressed invasion, spheroids formation ability and clonogenic potential of cancer cells. C4 showed synergistic anticancer effect when used in combination with palbociclib, JQ1 and paclitaxel in TNBC cells. Mechanistically, C4 inhibited cyclin-dependent kinase (CDK)4/6 pathway and targeted the expressions of MYC/STAT3/CCND1/CNNE1 axis. Furthermore, C4 suppressed the EMT signaling pathway that suggested a role of C4 in the inhibition of TNBC metastasis. Our findings may pave further in detailed mechanistic study on these complexes as potential chemotherapeutic agents in different types of human cancers.Copyright © 2024 Elsevier Inc. All rights reserved.