Rhodium(I) N-Heterocyclic Carbene Bioorganometallics as in Vitro Antiproliferative Agents with Distinct Effects on Cellular Signaling

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• 作者：Luciano Oehninger ; Sarah Spreckelmeyer ; Pavlo Holenya ; Samuel M. Meier ; Suzan Can ; Hamed Alborzinia ; Julia Schur ; Bernhard K. Keppler ; Stefan W?lfl ; Ingo Ott
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：December 24, 2015
• 年：2015
• 卷：58
• 期：24
• 页码：9591-9600
• 全文大小：505K
• ISSN：1520-4804

文摘

Organometallics with N-heterocyclic carbene (NHC) ligands have triggered major interest in inorganic medicinal chemistry. Complexes of the type Rh(I)(NHC)(COD)X (where X is Cl or I, COD is cyclooctadiene, and NHC is a dimethylbenzimidazolylidene) represent a promising type of new metallodrugs that have been explored by advanced biomedical methods only recently. In this work, we have synthesized and characterized several complexes of this type. As observed by mass spectrometry, these complexes remained stable over at least 3 h in aqueous solution, after which hydrolysis of the halido ligands occurred and release of the NHC ligand was evident. Effects against mitochondria and general cell tumor metabolism were noted at higher concentrations, whereas phosphorylation of HSP27, p38, ERK1/2, FAK, and p70S6K was induced substantially already at lower exposure levels. Regarding the antiproliferative activity in tumor cells, a clear preference for iodido over chlorido secondary ligands was noted, as well as effects of the substituents of the NHC ligand.