Synthesis and characterization of functionalized thymidine as a potential carrier for cisplatin-like drugs

Pursuing the idea of using a biological nanovector to drive the non-specific cytotoxic activity of Pt(II) complexes toward biological targets, we have singled out thymidine (T) as a potential biological carrier for delivery of cisplatin-like drugs to DNA. Thymidine was functionalized by first reacting it with solid sodium hydride and 1,3-diiodopropane, producing high yields of N3-iodopropylthymidine. Further reaction with ethylenediamine gave the bio-ligand N3-(3-ethylenediamine)propylthymidine which reacts in turn with K2PtCl4, resulting in a cisplatin-like nucleoside. This derivative (or more soluble analogues) can be phosphorylated by the cellular enzyme pool and incorporated into the growing DNA chain, thus making them suitable candidates as potential antiproliferative agents, exploiting both alkylating and antimetabolite mechanisms. (c) 2005 Elsevier B.V. All rights reserved.