轴向不对称抗肿瘤前药(OC-6-44)-乙酸二氨基二氯化羟基铂(IV)复合物2的生物学行为进行了深入研究，并与类似的对称Pt(IV)复合物1和3进行了比较，它们具有类似的结构。这些复合物在一组人类肿瘤细胞系上进行了测试。复合物2与它们的类似物1和3相比表现出异常的高细胞毒性（类似于顺铂）。它们的还原电位、还原动力学、亲脂性和膜亲和力进行了比较。在敏感的A2780人类卵巢癌细胞系和对应的耐药A2780cisR亚系中，深入研究了Pt(IV)复合物的细胞摄取和DNA铂基化。2的意外活性似乎与其独特的细胞累积有关，而不是与还原速率或DNA铂基化效能、凋亡诱导效率有所不同。尽管细胞摄取的确切机制尚未完全揭示，但一系列幼稚的实验表明出现了依赖能量的载体介导的转运：有机阳离子转运体（OCTs）是可能涉及的蛋白质。版权所有©2022年Elisabetta Gabano等。

The biological behavior of the axially unsymmetric antitumor prodrug (OC-6-44)-acetatodiamminedichloridohydroxidoplatinum(IV), 2, was deeply investigated and compared with that of analogous symmetric Pt(IV) complexes, namely, dihydroxido 1 and diacetato 3, which have a similar structure. The complexes were tested on a panel of human tumor cell lines. Complex 2 showed an anomalous higher cytotoxicity (similar to that of cisplatin) with respect to their analogues 1 and 3. Their reduction potentials, reduction kinetics, lipophilicity, and membrane affinity are compared. Cellular uptake and DNA platination of Pt(IV) complexes were deeply investigated in the sensitive A2780 human ovarian cancer cell line and in the corresponding resistant A2780cisR subline. The unexpected activity of 2 appears to be related to its peculiar cellular accumulation and not to a different rate of reduction or a different efficacy in DNA platination and/or efficiency in apoptosis induction. Although the exact mechanism of cell uptake is not fully deciphered, a series of naïve experiments indicates an energy-dependent, carrier-mediated transport: the organic cation transporters (OCTs) are the likely proteins involved.Copyright © 2022 Elisabetta Gabano et al.