Synthesis, DNA Binding and Antiviral Activity of New Uracil, Xanthine, and Pteridine Derivatives

• Published in: Archiv der Pharmazie (Weinheim) 2007-01, Vol.340 (1), p.26-31
• Main Authors: El-Sabbagh, Osama I., El-Sadek, Mohamed E., El-Kalyoubi, Samar, Ismail, Ibrahim
• Format: Article
• Language: English
• Subjects: 3-dimethyl-5-(substituted methylidene)aminouracil; 6-Amino-1; 6‐Amino‐1,3‐dimethyl‐5‐(substituted methylidene)aminouracil; Acyclovir - metabolism; Acyclovir - pharmacology; Animals; Antiviral activity; Antiviral Agents - chemical synthesis; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Cercopithecus aethiops; Cytopathogenic Effect, Viral - drug effects; DNA - metabolism; Molecular Structure; Peste-des-petits-ruminants virus - pathogenicity; Pteridines; Pteridines - chemical synthesis; Pteridines - metabolism; Pteridines - pharmacology; RNA - metabolism; Ruminantia; Synthesis; Uracil - analogs & derivatives; Uracil - chemical synthesis; Uracil - metabolism; Uracil - pharmacology; Vero Cells; Xanthines; Xanthines - chemical synthesis; Xanthines - metabolism; Xanthines - pharmacology
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.200600149

Some new 6‐amino‐1,3‐dimethyl‐5‐(substituted methylidene)aminouracils were synthesized. Most of them were cyclized with triethyl orthoformate as a one‐carbon source to afford 1,3‐dimethyl‐6‐substituted pteridine derivatives. Certain uracils gave xanthine instead of the expected pteridine derivatives upon using another one‐carbon source such as triethyl orthoacetate or triethyl orthobenzoate. The nucleic acid binding assay revealed that some new compounds showed high affinity, chelation, and fragmentation of nucleic acids whether DNA or RNA contrary to acyclovir that has affinity to DNA only. The antiviral activity of these novel compounds showed that compounds 2e and 2f reduced the cytopathogencity of Peste des petits ruminant virus (PPRV) on Vero cell culture by 60 and 50%, respectively.