BIS-NAPHTHALIMIDES .3. SYNTHESIS AND ANTITUMOR-ACTIVITY OF N,N'-BIS[2-(1,8-NAPHTHALIMIDO)-ETHYL] ALKANEDIAMINES

The bis-naphthalimides are a new class of antitumor agent. Previously, we have described initial synthetic series which established that two naphthalimide chromophores joined by polyamine linkers can produce ag ents with antitumor activity. We now extend these studies to describe the synthesis of a N,N'-bis[2-(1,8-naphthalimido)-ethyl]alkane diamine series and examine the alkyl linker and chromophore substitution requ irements for optimal antitumor activity. As a result, a bis-naphthalim idoethyl derivative with no chromophore substitution and a NH-(CH2)(3) -NH bridge was identified. This agent (LU 79553) had both potent cellu lar cytotoxicity (IC50 = 0.014 mu M) and was curative against MX-1 tum ors grown in athymic mice. It has now been selected for clinical devel opment.