Document Detail


Mixed ligand ruthenium(II) complexes of bis(pyrid-2-yl)-/bis(benzimidazol-2-yl)-dithioether and diimines: study of non-covalent DNA binding and cytotoxicity.
MedLine Citation:
PMID:  18399241     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of mixed ligand ruthenium(II) complexes [Ru(pdto)(diimine)](ClO4)2/(PF6)2 1-3 and [Ru(bbdo)(diimine)](ClO4), 4-6, where pdto is 1,8-bis(pyrid-2-yl)-3,6-dithiooctane, bbdo is 1,8-bis(benzimidazol-2-yl)-3,6-dithiooctane and diimine is 1,10-phenanthroline (phen), dipyrido-[3,2-d:2',3'-f]-quinoxaline (dpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz), have been isolated and characterised by analytical and spectral methods. The complexes [Ru(pdto)(phen)](PF6)2 la, [Ru(pdto)(dpq)(Cl](PF6) 2a, [Ru(bbdo)(phen)](PF6)2 4a and [Ru(bbdo)(dpq)](ClO4)2 5 have been structurally characterized and their coordination geometries around ruthenium(II) are described as distorted octahedral. In la, 4a and 5 the two thioether sulfur and two py/bzim nitrogen atoms of the tetradentate pdto/bbdo ligand are folded around Ru(II) to give predominantly a "cis-alpha" configuration. (I)H NMR spectral data of the complexes support this configuration in solution. In [Ru(pdto)(dpq)Cl](PF6) 2a with a distorted octahedral coordination geometry, one of the two py nitrogens of pdto is not coordinated. The DNA binding constants (Kb: 2, 2.00 +/- 0.02 x 10(4) M(-1), s = 1.0; 3, 3.00 +/- 0.01 x 10(6) M(-1), s = 1.3) determined by absorption spectral titrations of the complexes with CT DNA reveal that 3 interacts with DNA more tightly than 2 through partial intercalation of the extended planar ring of coordinated dppz with the DNA base stack. The DNA binding affinities of the complexes increase with increase in the number of planar aromatic rings in the co-ligand, and on replacing both the py moieties in pdto complexes (1-3) by bzim moieties to give bbdo complexes (4-6). Upon interaction with CT DNA the complexes 1, 2, 5 and 6 show a decrease in anodic current in the cyclic voltammograms. On the other hand, interestingly, 3 and 4 show an increase in anodic current suggesting their involvement in electrocatalytic guanine oxidation. Interestingly, of all the complexes, only 6 alters the superhelicity of DNA upon binding with supercoiled pBR322 DNA. The cytotoxicities of the dppz complexes 3 and 6, which avidly bind to DNA, have been examined by screening them against cell lines of different cancer origins. It is noteworthy that 6 exhibits selectivity with higher cytotoxicity against the melanoma cancer cell line (A375) than other cell lines, potency approximately twice that of cisplatin and toxicity to normal cells 3 and 90 times less than cisplatin and adriamycin respectively.
Authors:
Venugopal Rajendiran; Mariappan Murali; Eringathodi Suresh; Sarika Sinha; Kumaravel Somasundaram; Mallayan Palaniandavar
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Dalton transactions (Cambridge, England : 2003)     Volume:  -     ISSN:  1477-9226     ISO Abbreviation:  Dalton Trans     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-04-10     Completed Date:  2008-04-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101176026     Medline TA:  Dalton Trans     Country:  England    
Other Details:
Languages:  eng     Pagination:  148-63     Citation Subset:  IM    
Affiliation:
School of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents* / chemical synthesis,  chemistry,  pharmacology
Benzimidazoles / chemistry*
Binding, Competitive
Cell Line, Tumor
Cell Survival / drug effects
Crystallography, X-Ray
DNA / chemistry*
Humans
Ligands
Molecular Structure
Organometallic Compounds* / chemical synthesis,  chemistry,  pharmacology
Phenanthrolines / chemistry*
Quinoxalines / chemistry
Ruthenium / chemistry*
Sulfides / chemistry*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Benzimidazoles; 0/Ligands; 0/Organometallic Compounds; 0/Phenanthrolines; 0/Quinoxalines; 0/Sulfides; 66-71-7/1,10-phenanthroline; 7440-18-8/Ruthenium; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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