TY - JOUR
T1 - DNA binding and cytotoxicity of ruthenium(II) and rhenium(I) complexes of 2-amino-4-phenylamino-6-(2-pyridyl)-1,3,5-triazine
AU - Ma, Dik Lung
AU - Che, Chi Ming
AU - Siu, Fung Ming
AU - Yang, Mengsu
AU - Wong, Kwok Yin
N1 - This work was supported by the Areas of Excellence Scheme established under the University Grants Committee of the Hong Kong Special Administrative Region, China (AoE/P-10/01); The University of Hong Kong (University Development Fund); and the Research Grants Council of Hong Kong SAR, China (CityU 1189/01P).
PY - 2007/2/1
Y1 - 2007/2/1
N2 - [Ru(Bu2bpy)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 λ max = 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) × 10 4 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.
AB - [Ru(Bu2bpy)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 λ max = 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) × 10 4 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.
UR - http://www.scopus.com/inward/record.url?scp=33847096353&partnerID=8YFLogxK
U2 - 10.1021/ic061518s
DO - 10.1021/ic061518s
M3 - Journal article
C2 - 17257015
AN - SCOPUS:33847096353
SN - 0020-1669
VL - 46
SP - 740
EP - 749
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 3
ER -
