ABSTRACT
The crystal structures of 5-(5-furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (IV) and 5-(3-bromothien-2-yl)-2'-deoxyuridine (V) have been studied in order to explain the different affinity of the compounds for the herpes simplex virus type 1 (HSV-1) thymidine kinase. These compounds present a variable affinity according to the position of the heteroatom substituting the five-membered ring. An unfavourable substitution in the five-membered ring for interaction with the HSV-1 thymidine kinase has been identified.
Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/metabolism , Bromine , Deoxyuridine/chemistry , Deoxyuridine/metabolism , Herpesvirus 1, Human/enzymology , Thymidine Kinase/metabolism , Deoxyuridine/analogs & derivatives , Humans , Structure-Activity Relationship , Thiophenes/chemistry , Thiophenes/metabolism , X-Ray DiffractionABSTRACT
Structural and electronic characteristics of 5-(5-chlorothien-2-yl)-2'-deoxyuridine (I), 5-(furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (III), 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridine (V) and 5-(isoxazol-5-yl)-2'-deoxyuridine (IV) have been determined and compared to the BVDU (VI) characteristics in order to explain their respective affinity for the herpes simplex virus type 1 thymidine kinase (TK). Molecular structure of 5-(5-chlorothien-2-yl)-2'-deoxyuridine has been obtained using single crystal X-ray crystallography. Electrostatic potential maps, energy and topology of frontier orbitals were computed at the ab initio MO STO-3G and STO-3G level. These studies reveal that the electrostatic potential energy maps are clearly dependent on the affinity of the compound for the enzyme.