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使用体外癌症模型和多能干细胞对 Lepidiline A 及其金(I)、银(I)和铜(I)配合物进行合成与系统研究。

Synthesis and Systematic Investigation of Lepidiline A and Its Gold(I), Silver(I), and Copper(I) Complexes Using In Vitro Cancer Models and Multipotent Stem Cells.

作者信息

Tóth Szilárd, Szlávik Márton F, Mandel Réka, Fekecs Fanni, Tusnády Gábor, Vajda Flóra, Varga Nóra, Apáti Ágota, Bényei Attila, Paczal Attila, Kotschy András, Szakács Gergely

机构信息

Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar tudósok körútja 2, Budapest H-1117, Hungary.

Servier Research Institute of Medicinal Chemistry, Záhony utca 7, Budapest H-1031, Hungary.

出版信息

ACS Omega. 2024 Jul 15;9(29):32226-32234. doi: 10.1021/acsomega.4c05020. eCollection 2024 Jul 23.

DOI:10.1021/acsomega.4c05020
PMID:39072085
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11270681/
Abstract

The imidazole alkaloid lepidiline A from the root of has a moderate to low in vitro anticancer effect. Our aim was to extend cytotoxicity investigations against a panel of cancer cells, including multidrug-resistant cancer cells, and multipotent stem cells. Lepidiline A is a N-heterocyclic carbene precursor, therefore a suitable ligand source for metal complexes. Thus, we synthesized lepidiline A and its copper(I), gold(I), and silver(I) complexes and tested them against ovarian, gastrointestinal, breast, and uterine cancer cells and bone marrow-derived and adipose-derived mesenchymal stem cells. Lepidiline A and its copper complex demonstrated moderate cytotoxicity, while silver and gold complexes exhibited significantly enhanced and consistent cytotoxicity against both cancer and stem cell lines. ABCB1 in the multidrug-resistant uterine sarcoma line conferred significant resistance against lepidiline A and the copper-lepidiline A complex, but not against the silver and gold complexes. Our results indicate that only the copper complex induced a significant and universal increase in the production of reactive oxygen species within cells. In summary, binding of metal ions to lepidiline A results in enhanced cytotoxicity with the nature of the metal ion playing a critical role in determining its properties.

摘要

从[植物名称]根部提取的咪唑生物碱利皮地林 A 具有中度至低度的体外抗癌作用。我们的目的是扩大对一组癌细胞(包括多药耐药癌细胞)和多能干细胞的细胞毒性研究。利皮地林 A 是一种 N - 杂环卡宾前体,因此是金属配合物的合适配体来源。因此,我们合成了利皮地林 A 及其铜(I)、金(I)和银(I)配合物,并针对卵巢癌、胃肠道癌、乳腺癌和子宫癌细胞以及骨髓来源和脂肪来源的间充质干细胞对它们进行了测试。利皮地林 A 及其铜配合物表现出中度细胞毒性,而银和金配合物对癌细胞系和干细胞系均表现出显著增强且一致的细胞毒性。多药耐药子宫肉瘤细胞系中的 ABCB1 对利皮地林 A 和铜 - 利皮地林 A 配合物具有显著抗性,但对银和金配合物没有抗性。我们的结果表明,只有铜配合物能显著且普遍地诱导细胞内活性氧生成增加。总之,金属离子与利皮地林 A 的结合导致细胞毒性增强,金属离子的性质在决定其特性方面起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/241f16936eeb/ao4c05020_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/74440f5bcc77/ao4c05020_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/2a6997ad1144/ao4c05020_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/692dbe989e09/ao4c05020_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/13af4394846b/ao4c05020_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/5e77438933e9/ao4c05020_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/616a6bf88b48/ao4c05020_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/241f16936eeb/ao4c05020_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/74440f5bcc77/ao4c05020_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/2a6997ad1144/ao4c05020_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/692dbe989e09/ao4c05020_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/13af4394846b/ao4c05020_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/5e77438933e9/ao4c05020_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/616a6bf88b48/ao4c05020_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50c/11270681/241f16936eeb/ao4c05020_0004.jpg

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本文引用的文献

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