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带有 -Boc 保护的 α-氨基酸根抗衡离子的 NHC-Ag(I) 和 NHC-Au(I) 配合物对 MDA-MB-231 细胞的生长有强大影响。

NHC-Ag(I) and NHC-Au(I) Complexes with -Boc-Protected α-Amino Acidate Counterions Powerfully Affect the Growth of MDA-MB-231 Cells.

作者信息

Iacopetta Domenico, Costabile Chiara, La Chimia Marina, Mariconda Annaluisa, Ceramella Jessica, Scumaci Domenica, Catalano Alessia, Rosano Camillo, Cuda Giovanni, Sinicropi Maria Stefania, Longo Pasquale

机构信息

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy.

Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.

出版信息

ACS Med Chem Lett. 2023 Oct 10;14(11):1567-1575. doi: 10.1021/acsmedchemlett.3c00360. eCollection 2023 Nov 9.

Abstract

-Heterocyclic carbene (NHC) metal complexes are attracting scientists' interest as an alluring class of metallodrugs. Indeed, the versatile functionalization of NHC ligands makes them optimal scaffolds to be developed in medicinal chemistry. Besides, amino acids are great biological ligands for metals, such as silver and gold, even though their use is still under-investigated. Aiming to shed light on the anticancer properties of this kind of complex, we investigated a series of silver and gold complexes, stabilized by NHC ligands and bearing carboxylate salts of -butyloxycarbonyl (Boc)--protected glycine and l-phenylalanine as anionic ligands. The most active complexes, and , powerfully affect the growth of MDA-MB-231 breast cancer cells, with IC values in the low nanomolar range. Further studies demonstrated the blockade of the human topoisomerase I activity and actin polymerization reaction at 0.001 μM. These unique features make these complexes very interesting and worthy to be used for future studies.

摘要
  • 杂环卡宾(NHC)金属配合物作为一类诱人的金属药物正吸引着科学家们的关注。事实上,NHC配体的多功能官能团化使其成为药物化学中有待开发的理想骨架。此外,氨基酸是银和金等金属的优良生物配体,尽管其应用仍有待深入研究。为了阐明这类配合物的抗癌特性,我们研究了一系列由NHC配体稳定、并带有叔丁氧羰基(Boc)保护的甘氨酸和L-苯丙氨酸羧酸盐作为阴离子配体的银和金配合物。活性最高的配合物 和 能强烈影响MDA-MB-231乳腺癌细胞的生长,其IC值处于低纳摩尔范围。进一步研究表明,在0.001 μM浓度下,这些配合物可阻断人拓扑异构酶I的活性和肌动蛋白聚合反应。这些独特特性使得这些配合物非常有趣,值得用于未来的研究。

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Topoisomerase I inhibitors: Challenges, progress and the road ahead.拓扑异构酶I抑制剂:挑战、进展与未来之路。
Eur J Med Chem. 2022 Jun 5;236:114304. doi: 10.1016/j.ejmech.2022.114304. Epub 2022 Apr 2.

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