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DOI: 10.1039/A903293B (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1999, 3243-3252

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

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Adam Q. Siddiqui, Louise Merson-Davies and Paul M. Cullis

Abstract

Synthetic routes were developed to synthesise an N[hair space] 4-mono-derivatised spermidine–nitroimidazole conjugate and two novel structural isomers (N[hair space] 1- and N[hair space] 8-spermidine–nitroimidazole conjugates). A synthetic method was developed to synthesise an N[hair space] 1,N[hair space] 7-bis-derivatised norspermidine–nitroimidazole conjugate and further applied to the synthesis of an N[hair space] 1,N[hair space] 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[hair space] 1 > N[hair space] 8 ≈ N[hair space] 1, N[hair space] 8 > N[hair space] 4.

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