Benzothiazole bipyridine complexes of ruthenium(II) with cytotoxic activity.
A series of benzothiazole-substituted trisbipyridine ruthenium(II) analogues {[Ru(bpy)(2)(4,5'-bbtb)](2+), [Ru(bpy)(2)(5,5'-bbtb)](2+) and [Ru(bpy)(2)(5-mbtb)](2+) [bpy is 2,2'-bipyridine, bbtb is bis(benzothiazol-2-yl)-2,2'-bipyridine, 5-mbtb is 5-(benzothiazol-2-yl),5'-methyl-2,2'-bipyridine]} have been prepared and compared with the complex [Ru(bpy)(2)(4,4'-bbtb)](2+) reported previously. From the UV-vis spectral studies, substitution at the 5-position of the bpy causes the ligand-centred transitions to occur at considerably lower energy than for those with the functionality at the 4-position, while at the same time causing the emission to be effectively quenched. However, substitution at the 4-position causes the metal-to-ligand charge transfer to occur at lower energies. Fluorescent intercalator displacement studies indicate that the doubly substituted complexes displace ethidium bromide from a range of oligonucleotides, with the greater preference shown for bulge and hairpin sequences by the Lambda enantiomer. Since the complexes only show small variation in the UV-vis spectra on the introduction of calf thymus DNA and a small increase in fluorescence they do not appear to be intercalators, but appear to associate within one of the grooves. All of the reported bisbenzothiazole complexes show reasonable cytotoxicity against a range of human cancer cell lines.
Spillane
Caitriona B
CB
School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Belfast, UK.
Fletcher
Nicholas C
NC
Rountree
Sandra M
SM
van den Berg
Hendrik
H
Chanduloy
Severine
S
Morgan
Joy L
JL
Keene
F Richard
FR
D015082:2,2'-Dipyridyl; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007364:Intercalating Agents; D010084:Oxidation-Reduction; D017975:Ruthenium Compounds / Q000737:chemistry* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013057:Spectrum Analysis
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D007364:Intercalating Agents; D017975:Ruthenium Compounds; D015082:2,2'-Dipyridyl; D004247:DNA; C427203:calf thymus DNA