铂类化疗药物是治疗许多恶性肿瘤的基石。然而，它们的剂量限制性副作用促使人们努力开发对肿瘤组织具有更高选择性且副作用较少的新候选药物。在这里，我们开发了一种基于 Zeise 盐的细胞毒性铂 (II) 络合物，含有非甾体抗炎药乙酰水杨酸和丙氨酸作为配体 (4)。先前开发的配合物（5）对含硫生物分子表现出高反应性；因此，我们将重点放在结构稳定性的优化上。使用不同的氨基酸作为生物相容性螯合配体来实现这一目标。配位层的差异导致Zeise型前体1-3的稳定性发生显着变化。通过 N 在乙烯反位上与 L-Ala 配位显示出最有希望的结果，并用于稳定 5。因此，复合物 4 显示出改进的稳定性和细胞毒性，优于 5 和 1。

Platinum-based chemotherapeutics are a cornerstone in the treatment of many malignancies. However, their dose-limiting side effects have rooted efforts to develop new drug candidates with higher selectivity for tumor tissues and less problematic side effects. Here, we developed a cytotoxic platinum(II) complex based on Zeise's salt, containing the nonsteroidal anti-inflammatory drug acetylsalicylic acid and alanine as ligands (4). The previously developed complex (5) displayed high reactivity against sulfur-containing biomolecules; therefore, we put the focus on the optimization of the structure regarding its stability. Different amino acids were used as biocompatible chelating ligands to achieve this aim. Differences in the coordination sphere caused pronounced changes in the stability of Zeise-type precursors 1-3. Coordination with l-Ala through N in the trans position to ethylene showed the most promising results and was employed to stabilize 5. As a result, complex 4 showed improved stability and cytotoxicity, outperforming both 5 and 1.