Aminothiols linked to quinoline and acridine chromophores efficiently decrease 7,8-dihydro-8-oxo-2'-deoxyguanosine formation in gamma-irradiated DNA.
In a search for more active radioprotective compounds, we have prepared and examined a series of model molecules in which the radioprotective beta-aminothiol unit (free or derivatized as acetate or phosphorothioate) is tethered to the DNA-binding chromophores quinoline and acridine through links of variable length. The modifying activity of these 'hybrid' molecules was estimated by measuring the formation of 8-oxo-2'-deoxyguanosine (8-oxodGuo) in double-strand DNA upon exposure to gamma-rays in oxygen-free solution in the presence of the drugs. We show that all hybrid molecules protect the guanine moiety from oxidation more efficiently than the parent beta-aminothiol units. The degree of protection is the highest for the molecules in which the thiol is linked to the strong binding intercalator acridine through a long polyaminochain.
Laayoun
A
A
LEDSS, URA CNRS 332, Université Joseph Fourier, Grenoble, France.
Coulombeau
C
C
Constant
J F
JF
Berger
M
M
Cadet
J
J
Lhomme
J
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000166:Acridines / Q000737:chemistry; D004247:DNA / Q000378:metabolism / Q000528:radiation effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005720:Gamma Rays; D017665:Hydroxyl Radical; D007364:Intercalating Agents / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*
D000166:Acridines; D007364:Intercalating Agents; D011804:Quinolines; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; D017665:Hydroxyl Radical; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C037219:quinoline; D003849:Deoxyguanosine