Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

Bifunctional amine-tethered Ruthenium(II) arene complexes form monofunctional adducts on DNA

The tethered Ru-II half-sandwich complexes [eta(6):eta(1)-C6H5(CH2)(n)NH2)RuCl2] 1 (n = 3) and 2 (n = 2) have been synthesized as potential bifunctional anticancer complexes, and their X-ray crystal structures have been determined. They hydrolyze rapidly in aqueous solution to give predominantly mono-aqua mono-chlorido species. Mono-9EtG adducts, where 9EtG = 9-ethylguanine, form rapidly, but the second 9EtG binds more slowly and more weakly. In the X-ray crystal structure of the di-9EtG adduct [(eta(6):eta(1)-C6H5(CH2)(3)NH2)Ru(9EtG)(2)](CF3SO3)(2)center dot H2O (8 center dot H2O), one of the Ru-N7 bonds is significantly longer than the other (2.1588(18) vs 2.101(2) angstrom). The bound guanine bases adopt a head-to-head configuration, stabilized by tether NH2 hydrogen bonding to C60 of 9EtG. The X-ray crystal structure of the dinitrato complex [(eta(6):eta(1) -C6H5(CH2)(3)NH2)Ru(NO3)(2)] (3) showed both nitrates to be bound to ruthenium. This complex readily rutheniated calf thymus DNA but failed to produce stop sites on pSP73KB plasmid DNA during DNA transcription by an RNA polymerase. This suggested that only monofunctional DNA adducts formed, as did interstrand cross-linking assays. Also, the unwinding angle induced in negatively supercoiled DNA (9 +/- 1 degrees) was less than that induced by cisplatin (13 degrees). These findings may explain why complexes such as 1 and 2 exhibited low cytotoxicities (IC50 values >100 mu M) toward A2780 human ovarian cancer cells

The complete sequence of the yeast chromosome III.

The entire DNA sequence of chromosome III of the yeast Saccharomyces cerevisiae has been determined. This is the first complete sequence analysis of an entire chromosome from any organism. The 315-kilobase sequence reveals 182 open reading frames for proteins longer than 100 amino acids, of which 37 correspond to known genes and 29 more show some similarity to sequences in databases. Of 55 new open reading frames analysed by gene disruption, three are essential genes; of 42 non-essential genes that were tested, 14 show some discernible effect on phenotype and the remaining 28 have no overt function

Complete DNA sequence of yeast chromosome XI.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined. In addition to a compact arrangement of potential protein coding sequences, the 666,448-base-pair sequence has revealed general chromosome patterns; in particular, alternating regional variations in average base composition correlate with variations in local gene density along the chromosome. Significant discrepancies with the previously published genetic map demonstrate the need for using independent physical mapping criteria.0Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe