DNA AFFINITY OF NEW AMINOTHIOLOXAZOLOPYRIDOCARBAZOLE DERIVATIVES DETERMINED BOTH IN-VITRO AND IN SINGLE LIVING CELLS

New potential DNA radioprotective agents were obtained by coupling an oxazolopyridocarbazole nucleus (NMHE) to simple aminothiol molecules s uch as cystine, cysteamine and WR2721. The ability of the new adducts to compete with ethidium bromide DNA binding was determined through th eir IC50 values which ranged between 1.4 and 2.75 x 10(-6) mol.dm(-3), whereas for aminothiols IC50 ranged between 3 and 6 x 10(-3) mol.dm(- 3). Similarly, the apparent DNA-binding constants for aminothiol-OPCs were found to be 200-1000 fold higher than far parent molecules. The a pparent DNA binding constants of the adducts was strongly influenced b y the medium ionic strength, which suggests that ionic interactions oc cur in the overall binding process. Microspectrofluorometric analysis of drug intracellular localization in SC10 living cells revealed that aminothiol-OPCs were specifically accumulated in the cell nucleus.