Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 46, Issue 5, Pages 1555-1563Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2011.01.074
Keywords
Ruthenium complexes; 2,2 '-Biimidazole; Apoptosis; Anti-metastatic; CDK inhibitors
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Funding
- 973 Program of China [2007CB815306]
- National Natural Science Foundation of China [20871056]
- Fundamental Research Funds for the Central Universities
- Natural Science Foundation of Guangdong Province [8251063201000008]
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Two new ruthenium complexes, trans,cis,cis-[RuCl2(DMSO)(2)(H(2)biim)] (1) and mer-[RuCl3(DMSO) (H(2)biim)] (2) (DMSO = dimethyl sulfoxide and H(2)biim = 2,2'-biimidazole), have been synthesized and fully characterized by single-crystal X-ray analysis. The less stable complex 2 is more cytotoxic against the four human cancer cell lines tested than 1. Further studies show that 1 and 2 exhibit cell growth inhibition by triggering G0/G1 cell cycle arrest and mitochondria-mediated apoptosis. Additionally, complex 2 exerts potent inhibitory effects on the adhesion and migration of human cancer cells comparable to that of NAMI-A ([ImH][trans-[RuCl4(Im)(DMSO-S)], Im = imidazole). Target validation studies show that cyclin-dependent kinases (CDKs), other than DNA, are more likely to be targets of 1 and 2. (C) 2011 Elsevier Masson SAS. All rights reserved.
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