Platinum-based anticancer drugs are one of the most widely used anticancer chemotherapeutics in oncology. Lonidamine (LND) could increase the response of human tumor cells to platinum(II) drugs in preclinical studies by working on the mitochondria. Herein, five platinum(IV) prodrugs conjugated with their potentiator LND are prepared, and most of the target complexes achieve improved anticancer activities compared with their platinum(II) precursors. Notably, Pt(NH₃)₂(LND)Cl₃ (complex 1) derived from cisplatin achieve significantly improved anticancer activities against LNCaP cells and could trigger cancer cell death via an apoptotic pathway and the cell cycle arrest mainly at S phases. And the induction of apoptosis by complex 1 in LNCaP cells is closely associated with mitochondrial function disruption and reactive oxygen species (ROS) accumulation. Moreover, it is possessed of the ability to overcome cisplatin-resistance. Further research revealed that complex 1 could be easily reduced to release its platinum(II) precursor and axial ligand by ascorbic acid. All the results provid evidence to support the design strategy of conjugating platinum complexes with its potentiator to improve their anticancer effect.

铂基抗癌药是肿瘤学中使用最广泛的抗癌化学疗法之一。在临床前研究中，Lonidamine（LND）可通过研究线粒体来增加人类肿瘤细胞对铂（II）药物的反应。在此，制备了五种与其增效剂LND偶联的铂（IV）前药，与它们的铂（II）前体相比，大多数目标复合物均具有更高的抗癌活性。值得注意的是，衍生自顺铂的Pt（NH ₃）₂（LND）Cl ₃（复合物1）显着提高了对LNCaP细胞的抗癌活性，并可能通过凋亡途径触发癌细胞死亡，并且细胞周期主要停留在S期。并通过复合物诱导细胞凋亡LNCaP细胞中的1与线粒体功能破坏和活性氧（ROS）积累密切相关。此外，它具有克服顺铂耐药性的能力。进一步的研究表明，复合物1可以很容易地被抗坏血酸还原以释放其铂（II）前体和轴向配体。所有结果均提供证据支持将铂配合物与其增效剂结合以改善其抗癌作用的设计策略。