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

摘要

Synthetic routes were developed to synthesise an N~4-mono-derivatised spermidine-nitroimidazole conjugate and two novel structural isomers (N~1- and N~8-spermidine-nitroimidazole conjugates). A synthetic method was developed to synthesise and N~1, N~7-bis-derivatised norspermidine-nitroimidazole conjugate and further applied to the synthesis of an N~1, N~8-bis-derivatised spermidine-nitroimidazole conjugate. The compounds were examined for their ability to serve as substrates for the polyamine uptake system in A549 lung carcinoma cells, by measuring their inhibition of [~(14)C]spermidine uptake. Marked differences were observed between the nitroimidazole-polyamine conjugates. For maximum recognition as a substrate by the polyamine transport system, the aminobutyl unit of spermidine should remain underivatised. The preferred site(s) for spermidine amino derivatisation was in the order: N~1 > N~8 = N~1, N~8 > N~4.