DNA as a possible target for antitumor ruthenium(III) complexes.
The interaction of two experimental ruthenium(III)-containing antitumor complexes-Na[trans-RuCl(4)(DMSO)(Im)] (NAMI) and dichloro(1,2-propylendiaminetetraacetate)ruthenium(III) (RAP)-with DNA was investigated through a number of spectroscopic and molecular biology techniques, including spectrophotometry, circular dichroism, gel shift analysis, and restriction enzyme inhibition. It was found that both complexes slightly alter DNA conformation, modify its electrophoretic mobility, and inhibit DNA recognition and cleavage by some restriction enzymes, though they were less effective than cisplatin in producing such effects. Notably, the effects produced by NAMI on DNA were much larger than those induced by RAP. Implications of these results for the mechanism of action of ruthenium(III) antitumor complexes are discussed.
Gallori
E
E
Department of Chemistry, University of Florence, Florence, 50121, Italy.
Vettori
C
C
Alessio
E
E
Vilchez
F G
FG
Vilaplana
R
R
Orioli
P
P
Casini
A
A
Messori
L
L
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004262:DNA Restriction Enzymes / Q000037:antagonists & inhibitors; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives / Q000494:pharmacology; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D009942:Organometallic Compounds / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects / Q000235:genetics; D012428:Ruthenium / Q000494:pharmacology*; D017975:Ruthenium Compounds
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); C109683:propylene-1,2-diaminotetraacetic acid-ruthenium(III) complex; D012428:Ruthenium; D004247:DNA; D004492:Edetic Acid; D004262:DNA Restriction Enzymes; D004121:Dimethyl Sulfoxide