CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, CZ-62500 Brno, Czechia.
Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, CZ-62500 Brno, Czechia.
Inorg Chem. 2021 Dec 6;60(23):17911-17925. doi: 10.1021/acs.inorgchem.1c02467. Epub 2021 Nov 5.
Platinum-based anticancer drugs are actively developed utilizing lipophilic ligands or drug carriers for the efficient penetration of biomembranes, reduction of side effects, and tumor targeting. We report the development of a supramolecular host-guest system built on cationic platinum(II) compounds bearing ligands anchored in the cavity of the macrocyclic host. The host-guest binding and hydrolysis process on the platinum core were investigated in detail by using NMR, MS, X-ray diffraction, and relativistic DFT calculations. The encapsulation process in cucurbit[7]uril unequivocally promotes the stability of hydrolyzed dicationic -[Pt(NH)(HO)(NH-R)] compared to its isomer. Biological screening on the ovarian cancer lines A2780 and A2780/CP shows time-dependent toxicity. Notably, the reported complex and its β-cyclodextrin (β-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@β-CD, respectively, while maintaining a significantly lower toxicity profile.
铂类抗癌药物正在利用亲脂性配体或药物载体积极开发，以实现生物膜的有效穿透、减少副作用和肿瘤靶向。我们报告了一种基于阳离子铂(II)化合物的超分子主客体系统的开发，该化合物的配体锚固在大环主体的腔中。通过使用 NMR、MS、X 射线衍射和相对论 DFT 计算，详细研究了铂核上的主客体结合和水解过程。在 cucurbit[7]uril 中的包封过程明确促进了水解的二价阳离子 -[Pt(NH)(HO)(NH-R)]的稳定性，与异构体相比。对卵巢癌细胞系 A2780 和 A2780/CP 的生物筛选显示出时间依赖性毒性。值得注意的是，报道的配合物及其 β-环糊精 (β-CD) 组装体分别实现了与顺铂和 cisplatin@β-CD 相同的细胞摄取，同时保持显著较低的毒性特征。
