Anticancer drug IUdR and other 5-halogen derivatives of 2 '-deoxyuridine: conformers, hydrates, and structure-activity relationships

作者：Alcolea Palafox M

来源：Structural Chemistry, 2014, 25(1): 53-69.

DOI：10.1007/s11224-013-0225-1

• IUdR
• 5-iodo-2 '-deoxyuridine
• Antiviral agents
• Anticancer drug
• Nucleoside analog

The effect of hydration on the molecular structure and energetics of the most stable conformers of the nucleoside analog 5-iodo-2'-deoxyuridine (IUdR) was carried out. To simulate the first hydration shell, two models were considered: the PCM model and the Discrete model (DM), including a variable number (1-20) of explicit water molecules surrounding the nucleoside. More than two hundred hydrated structures with water were analyzed by B3LYP and MP2 quantum chemical methods. Conformer B1 (syn-gg-gg) is the most stable by B3LYP and MP2, in the isolated state and in the first hydration shell. The CP-corrected formation and interaction energies for IUdR and water molecules were determined. The effect of the hydration on the total atomic charges and intermolecular distances were also discussed. 5-fluoro- (FUdR), 5-chloro- (ClUdR), and 5-bromo- (BrUdR) 2'-deoxyuridine derivatives were full optimized, and the effect of the halogen atom on the molecular structure was analyzed. In these, three derivatives was simulated the first hydration shell with 20 explicit water molecules within the DM. Several relationships/tendencies structure-activity were established that can help for the design of new drugs.

• 出版日期2014-2