当前位置： SCI文献检索 > JOURNAL OF INORGANIC BIOCHEMISTRY期刊下所有文献 > Trans-cis-cis-[RuCl2(DMSO)2(2-amino-5-methyl-thiazole)2], (PMRu52), a novel ruthenium(II) compound acting as a strong inhibitor of cathepsin B.

Trans-cis-cis-[RuCl2(DMSO)2(2-amino-5-methyl-thiazole)2], (PMRu52), a novel ruthenium(II) compound acting as a strong inhibitor of cathepsin B.

Abstract：

:A novel ruthenium(II) compound, trans-cis-cis-[Ru(II)Cl(2)(DMSO)(2)(2-amino-5-methyl-thiazole)(2)], (I), PMRu52 hereafter, that may be obtained from the previously described (cis and trans)-[Ru(II)Cl(2)(DMSO)(4)] complexes, was designed, synthesized and characterised. The single crystal X-ray structure shows a roughly regular octahedral environment for the ruthenium(II) center with the two chloride ligands in trans and the other two pairs of identical ligands in cis. The behaviour of PMRu52 in phosphate buffer, at pH=7.4, was characterised spectroscopically as well as its interactions with a few representative biomolecules. Tight ruthenium binding to serum albumin was established by joint use of spectroscopic and separation methods. Afterward, the reactions of PMRu52 with the model proteins ubiquitin and cytochrome c were monitored through electrospray ionisation mass spectrometry (ESI-MS) methods: the formation of metallodrug-protein adducts was documented in detail and the fragmentation patterns of PMRu52 were defined. Finally, the ability of PMRu52 to affect the activity of cathepsin B, a well known cysteine protease, was evaluated in vitro and a pronounced enzyme inhibition highlighted, with an IC(50) value of 5.5 muM. This latter finding is of particular interest as cathepsin B constitutes an attractive "druggable" target for cancer, rheumatoid arthritis and other important diseases.

journal_name

J Inorg Biochem

journal_title

Journal of inorganic biochemistry

authors

Mura P,Camalli M,Casini A,Gabbiani C,Messori L

doi

10.1016/j.jinorgbio.2009.10.002

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

111-7

issue

2

eissn

0162-0134

issn

1873-3344

pii

S0162-0134(09)00250-5

journal_volume

104

pub_type

杂志文章

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