二羧基白铂(II)-NHC配合物在细菌幽灵中的负载作为癌症治疗的最新进展

IF 3.6 3区 医学 Q2 CHEMISTRY, MEDICINAL
Amelie Scherfler, Klaus Wurst, Stefan Schwaiger, Francesco Baschieri, Martin Hermann, Daniel Baecker, Irena Pashkunova-Martic, Brigitte Kircher, Hristo P. Varbanov
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引用次数: 0

摘要

本研究旨在改善以苯并咪唑为基础的Pt(II)- n -杂环碳(NHC)配合物的药物样性质,特别是通过提高其水溶性和向癌细胞的递送。因此,制备了4个新的具有单齿羧基配体的苯并咪唑-2-吡啶型Pt(II)配合物,并通过光谱和晶体学相结合的方法证实了它们的结构。通过1H NMR谱和HPLC-MS分析考察了其在水溶液和细胞培养基中的稳定性。使用MTT法评估卵巢癌细胞系(A2780wt(顺铂敏感)和A2780cis(顺铂耐药))和非癌性骨髓基质细胞系(HS-5)的细胞毒性。大多数复合物表现出与卡铂相当或超过卡铂的细胞毒性,对癌细胞具有优先活性。将所有四种Pt(II)复合物加载到两种不同的非致病性菌株大肠埃希菌Nissle 1917和大肠埃希菌NM522的细菌鬼细胞(BGs)中,显著增强了细胞内积累和细胞毒性。此外,机制研究表明,所有测试的化合物,无论配方,诱导细胞凋亡。它们引发免疫原性细胞死亡的潜力也被评估,尽管只在选定的标志上观察到适度的影响。总的来说,这些发现突出了二羧基铂(II)-NHC配合物的潜力,特别是加载到基于bg的配方中,作为有希望的抗癌候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Loading of Dicarboxylatoplatinum(II)-NHC Complexes in Bacterial Ghosts as an Advanced Development in Cancer Therapy

Loading of Dicarboxylatoplatinum(II)-NHC Complexes in Bacterial Ghosts as an Advanced Development in Cancer Therapy

This study aimed to improve the drug-like properties of benzimidazole-based Pt(II)-N-heterocyclic carbene (NHC) complexes, particularly by enhancing their water solubility and delivery to cancer cells. Accordingly, four new Pt(II) complexes of the benzimidazol-2-ylidene type, featuring monodentate carboxylato ligands, were prepared and their structures confirmed through a combination of spectroscopic and crystallographic techniques. Their stability in aqueous solution and cell culture medium was investigated by 1H NMR spectroscopy and HPLC-MS analysis. Cytotoxicity was assessed using the MTT assay in ovarian cancer cell lines (A2780wt (cisplatin sensitive) and A2780cis (cisplatin resistant)) and a noncancerous bone marrow stromal cell line (HS-5). Most complexes exhibited cytotoxicity comparable to or exceeding that of carboplatin, with preferential activity toward cancer cells. Loading of all four Pt(II) complexes into bacterial ghost cells (BGs) derived from two different nonpathogenic bacterial strains, Escherichia coli (E. coli) Nissle 1917 and E. coli NM522 notably enhanced the intracellular accumulation and cytotoxicity. Furthermore, mechanistic studies demonstrated that all tested compounds, regardless of formulation, induced apoptosis. Their potential to trigger immunogenic cell death was also evaluated, though only a modest effect was observed on selected hallmarks. Collectively, these findings highlight the potential of dicarboxylatoplatinum(II)-NHC complexes, particularly loaded into BG-based formulations, as promising anticancer drug candidates.

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来源期刊
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
期刊介绍: Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
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