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筛选过渡金属氨基甲酸酯的生物性质表明金(I)和银(I)配合物具有很强的细胞毒性和抗菌活性。

Screening the biological properties of transition metal carbamates reveals gold(I) and silver(I) complexes as potent cytotoxic and antimicrobial agents.

机构信息

University of Pisa, Department of Chemistry and Industrial Chemistry, Via G. Moruzzi 13, I-56124 Pisa, Italy.

University of Burgos, Department of Chemistry, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain.

出版信息

J Inorg Biochem. 2022 Feb;227:111667. doi: 10.1016/j.jinorgbio.2021.111667. Epub 2021 Nov 18.

Abstract

We report a screening study aimed to assess for the first time the air- and water-stability and the biological potential of simple metal-carbamates. These molecular metallic species are based on elements belonging to the groups 4-5, 7-9 and 11, and tin, and are easily available from inexpensive reagents. Complexes [Ag(OCNEt)] (13-Ag) and [Au(OCNMe)(PPh)] (14-Au) resulted substantially stable in aqueous media and exhibited a potent in vitro cytotoxicity. Especially 13-Ag revealed a significant selectivity against the A549 lung adenocarcinoma and the A2780 ovarian cancer cell lines with respect to the noncancerous HEK293 cell line. Generation of ROS (reactive oxygen species) and mitochondrial membrane depolarization were recognized for 13-Ag and 14-Au; notwithstanding, the cell death mechanism is different in the two cases: apoptosis and cell cycle arrest in G0/G1 phase for 13-Ag; necroptosis and cell cycle arrest in S phase for 14-Au. Both 13-Ag and 14-Au are endowed with antibacterial activity, which is relatively stronger for 13-Ag towards Gram negative and for 14-Au towards Gram positive strains, respectively.

摘要

我们报告了一项筛选研究,旨在首次评估简单金属氨基甲酸盐的空气和水稳定性以及生物潜力。这些分子金属物种基于属于第 4-5、7-9 和 11 族以及锡的元素,并且可以从廉价试剂中轻松获得。配合物 [Ag(OCNEt)] (13-Ag) 和 [Au(OCNMe)(PPh)] (14-Au) 在水介质中基本稳定,并表现出很强的体外细胞毒性。特别是 13-Ag 对非癌细胞系 HEK293 具有显著的选择性,对肺腺癌 A549 细胞系和卵巢癌细胞系 A2780 具有显著的选择性。对于 13-Ag 和 14-Au,我们发现其能够产生 ROS(活性氧)和线粒体膜去极化;尽管如此,两种情况下的细胞死亡机制是不同的:13-Ag 为细胞凋亡和 G0/G1 期细胞周期停滞;14-Au 为细胞坏死和 S 期细胞周期停滞。13-Ag 和 14-Au 都具有抗菌活性,对于革兰氏阴性菌,13-Ag 的活性相对较强,对于革兰氏阳性菌,14-Au 的活性相对较强。

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