Synthesis, Biological Activity, and Structure−Activity Relationships for Potent Cytotoxic Rhodium(III) Polypyridyl Complexes

详细信息    查看全文

• 作者：Melanie Harlos ; Ingo Ott ; Ronald Gust ; Hamed Alborzinia ; Stefan Wö ; lfl ; Anna Kromm ; William S. Sheldrick
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：July 10, 2008
• 年：2008
• 卷：51
• 期：13
• 页码：3924 - 3933
• 全文大小：1606K
• 年卷期：v.51,no.13(July 10, 2008)
• ISSN：1520-4804

文摘

The complexes mer-[RhCl₃(DMSO-κS)(pp)] 1a−5a may be prepared by reaction of mer,cis-[RhCl₃(DMSO-κS)₂(DMSO-κO)] with the appropriate polypyridyl ligand (pp = bpy, phen, dpq, dppz, dppn) in CH₃OH/H₂O solution at 75 °C. The mer isomers of 1a−5a are stable in chloroform solution but those of 1a and 2a isomerize rapidly to a mixture of fac and mer isomers in DMSO. The complexes are potent in vitro cytotoxic agents and exhibit IC₅₀ values that are strongly dependent on the size of the polypyridyl ligand. IC₅₀ values of, respectively, 4.0 (0.5) and 1.9 (0.5), 0.40 (0.06) and 0.19 (0.05), and 0.079 (0.012) and 0.069 (0.021) µM are observed for 1a−3a against the human cell lines MCF-7 (breast cancer) and HT-29 (colon cancer). Cellular uptake studies showed a rapid and high accumulation of the polypyridyl compounds. Treatment of HT-29 and MCF-7 cells with 3a leads to significant decreases in cellular oxygen consumption and the rate of extracellular acidification.