Two spin labeled triazenes: relationship between biochemical and biological activities.

Biochemical and biological activities of two recently synthesized spin labeled triazenes, containing the nitroxyl free radical moiety at different places of the triazene structure have been studied and compared with those of the antitumor drug Dacarbazine (DTIC). Tissue distribution of the triazenes was investigated in vitro in organ homogenates, tumor (B16 melanoma) and blood of C57BL mice using the electron paramagnetic resonance (EPR) method. The spin labeled triazenes were mainly localized in the tumor and in the brain. Normal leucocites, YAC-1 mNK target Moloney lymphoma cells and B16 melanoma cells were treated with spin labeled triazenes in vitro and the effects on cell viability were compared. Spin labeled 3,3-dimethyl triazene with nitroxyl radical as a substituent in the benzen ring was more cytotoxic to B16 melanoma cells than to YAC-1 Moloney lymphoma cells and normal leucocites in comparison to the spin labeled monomethyl triazene. The spin labeled derivatives were assessed with low toxicity for BDF1 mice hybrids in vivo. These results could be interpreted in terms of a possible correlation between tissue distribution and the selective antimelanoma activity of the spin labeled triazenes. Copyright 2002 Elsevier Science B.V.