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一种新型 4-(吡啶基)-4H-苯并[g]色烯-5,10-二酮钌(II)复合物可诱导 518A2 黑素瘤细胞衰老。

A new 4-(pyridinyl)-4H-benzo[g]chromene-5,10-dione ruthenium(II) complex inducing senescence in 518A2 melanoma cells.

机构信息

Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95440, Bayreuth, Germany.

Department of Chemistry, Abeda Inamdar Senior College, 2390-B, K.B. Hidayatullah Road, Pune, 411001, India.

出版信息

J Biol Inorg Chem. 2019 Aug;24(5):647-657. doi: 10.1007/s00775-019-01677-y. Epub 2019 Jun 19.

Abstract

2-Amino-5,10-dihydro-5,10-dioxo-4(pyridine-3-yl)-4H-benzo[g]chromene-3-carbonitrile 5, a cytotoxic lawsone derivative, was reacted with [Ru(p-cymene)Cl] to afford a new Ru(II) 'piano-stool' complex 6 which differed from its ligand 5 by a greater selectivity for highly invasive 518A2 melanoma cells over human dermal fibroblasts in MTT cytotoxicity assays, and by inducing senescence rather than apoptosis in the former. DNA is a likely cellular target of complex 6 as it bound, presumably non-covalently, to linear and circular double-stranded DNA in vitro and as ruthenium was found in the lysate of nuclei of treated 518A2 melanoma cells. It also caused a fivefold increase of reactive oxygen species in these cells, originating from a more persistent redox cycling as visualised by cyclic voltammetry.

摘要

2-氨基-5,10-二氢-5,10-二氧代-4(吡啶-3-基)-4H-苯并[g]色烯-3-甲腈 5 是一种细胞毒性的 lawsone 衍生物,与 [Ru(p-cymene)Cl] 反应得到了一种新的 Ru(II)“钢琴凳”配合物 6,与配体 5 相比,该配合物对高度侵袭性的 518A2 黑色素瘤细胞具有更高的选择性,而对人真皮成纤维细胞的选择性较低。在 MTT 细胞毒性试验中,该配合物诱导 518A2 黑色素瘤细胞衰老而不是凋亡。由于配合物 6 可能非共价结合到体外的线性和环状双链 DNA 上,并且在处理过的 518A2 黑色素瘤细胞核的裂解物中发现了钌,因此 DNA 可能是该配合物的细胞靶标。它还导致这些细胞中活性氧的五倍增加,这源自于通过循环伏安法可视化的更持久的氧化还原循环。

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