Anticancer Ruthenium(畏6-p-cymene) Complexes of Nonsteroidal Anti-inflammatory Drug Derivatives
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- 作者：Farhana Aman ; Muhammad Hanif ; Waseeq Ahmad Siddiqui ; Adnan Ashraf ; Lukas K. Filak ; J贸hannes Reynisson ; Tilo S枚hnel ; Stephen M. F. Jamieson ; Christian G. Hartinger
- 刊名：Organometallics
- 出版年：2014
- 出版时间：October 13, 2014
- 年：2014
- 卷：33
- 期：19
- 页码：5546-5553
- 全文大小：448K
- ISSN：1520-6041
文摘
Oxicams are a versatile family of heterocyclic compounds, and the two representatives meloxicam and piroxicam are widely used drugs for the treatment of a variety of inflammatory and rheumatic diseases in humans. As cancer-associated inflammation is known to occur in carcinogenesis, we aimed to combine compounds carrying bioactive oxicam moieties with ruthenium(arene) fragments, known for anticancer activity. RuII(arene) complexes with methyl ester derivatives of the oxicam scaffold were prepared and characterized by standard methods and crystallographically. The organoruthenium compounds formed from RuII(畏6-p-cymene) chlorido moieties and oxicam-based ligands were subjected to bioanalytical investigations to establish their physicochemical properties with regard to stability in DMSO and water as well as reactivity toward the amino acids l-histidine (His), l-methionine (Met), and l-cysteine (Cys) and the DNA model compound guanosine 5鈥?monophosphate (5鈥?GMP). The compounds hydrolyzed rapidly in water to give the respective aqua complexes, formed amino acid complexes with Met and His, but decompose with Cys, while interaction with 5鈥?GMP was through its phosphate residue. The anticancer activity of the complexes against the colon carcinoma HCT116 and breast cancer MDA MB 231 cancer cell lines was established using an in vitro assay. The cytotoxicity was found strongly dependent on the lipophilicity of the compound, as was shown through correlation with log kw and clog P values of the ligands. The most lipophilic compound [chlorido(methyl 4-oxido-2-benzyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide)(畏6-p-cymene)ruthenium(II)] was the most active in the cell assays, with an IC50 of 80 渭M in HCT116 cells.