Synthesis and biological activity of carbocyclic lexitropsins with a bioreductive fragment.

Carbocyclic oligopeptides containing of two, three or four aromatic rings with N,N-dimethylpropyl-1,3-diamine group as C-terminus fragment of compounds and 5-[bis(2-chloroethyl)amino]-2,4-dinitrobenzamide as N-terminal were synthesized. These lexitropsins present antitumour activity on the neoplastic cells hepatoblastoma HEP G2. These experiments were evaluated in hypoxic and oxygen conditions. Significant differences of activity in oxygen and hypoxic conditions were shown only in compound, N-(3-dimethylaminopropyl)-N'-([3-[5-bis(2-chlorethyl)amino]-2,4-dinitrobenzamide])-phenyl]urea dihydrochloride 1 (IC50 = 8545 nM in oxygen vs. IC50 = 710 nM in hypoxia). The rest of compounds (2-6) do not indicate differences of activity in oxygen and hypoxia.