The synthesis of novel polyamine-nitroimidazole conjugates designed to probe the structural specificities of the polyamine uptake system in A549 lungcarcinoma cells

Synthetic routes were developed to synthesise an N-4-mono-derivatised sperm idine-nitroimidazole conjugate and two novel structural isomers (N-1- and N -8-spermidine-nitroimidazole conjugates). A synthetic method was developed to synthesise an N-1,N-7-bis-derivatised norspermidine-nitroimidazole conju gate and further applied to the synthesis of an N-1,N-8-bis-derivatised spe rmidine-nitroimidazole conjugate. The compounds were examined for their abi lity to serve as substrates for the polyamine uptake system in A549 lung ca rcinoma cells, by measuring their inhibition of [C-14]spermidine uptake. Ma rked differences were observed between the nitroimidazole-polyamine conjuga tes. For maximum recognition as a substrate by the polyamine transport syst em, the aminobutyl unit of spermidine should remain underivatised. The pref erred site(s) for spermidine amino derivatisation was in the order: N-1 > N -8 approximate to N-1, N-8 > N-4.