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DNA Binding and Cytotoxicity of Ruthenium(II) and Rhenium(I) Complexes of 2-Amino-4-phenylamino-6-(2-pyridyl)-1,3,5-triazine

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posted on 05.02.2007, 00:00 by Dik-Lung Ma, Chi-Ming Che, Fung-Ming Siu, Mengsu Yang, Kwok-Yin Wong
[Ru(tBu2bpy)2(2-appt)](PF6)2 [1·(PF6)2, tBu2bpy = 4,4‘-di-tert-butyl-2,2‘-bipyridine, 2-appt = 2-amino-4-phenylamino-6-(2-pyridyl)-1,3,5-triazine] and [Re(CO)3(2-appt)Cl] (2) were prepared and characterized by X-ray crystal analysis. The binding of 1·(PF6)2 and 2 to calf thymus DNA (ct DNA) led to increases in the DNA melting temperature (ΔTm = +12 °C), modest hypochromism (29% and 5% of the absorption bands at λmax = 450 and 376 nm, respectively), and insignificant shifts in the absorption maxima. The binding constants of 1·(PF6)2 and 2 with ct DNA, as determined by absorption titration, are (8.9 ± 0.5) × 104 and (3.6 ± 0.1) × 104 dm3 mol-1, respectively. UV−vis absorption titration, DNA melting studies, and competition dialysis using synthetic oligonucleotides [poly(dA−dT)2 and poly(dG−dC)2] revealed that 1·(PF6)2 and 2 exhibit a binding preference for AT sequences. A modeling study on the interaction between 1 or 2 and B-DNA revealed that the minor groove is the most favored binding site and an extensive hydrogen-bonding network is formed. As determined by MTT assays, 1·(PF6)2 and 2 exhibited moderate cytotoxicities toward several human cancer cell lines (KB-3-1, HepG2, and HeLa), as well as a multi-drug-resistant cancer cell line (KB-V-1). According to confocal microscopic and flow cytometric studies, 1·(PF6)2 and 2 induced apoptosis (50−60%) in cancer cells with <5% necrosis detected.

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