The synthesis of novel polyamine–nitroimidazole conjugates designed to probe the structural specificities of the polyamine uptake system in A549 lung carcinoma cells
Abstract
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 an 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 [14C]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.