Comparation interferon- inducing and antiviral properties of 2-amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), tilorone hydrochloride, and polyinosinic-polycytidylic acid.
2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), polyinosinic acid-polycytidylic acid [poly(I:C)], and tilorone HCl induced high levels of serum interferon in mice. Each consequently protected mice against infection with several viruses. After daily injection of inducer, mice developed a reduced interferon response (hyporeactivity) to each compound. However, hyporeactivity developed more slowly to U-25,166 and poly(I:C) than to tilorone HCl. After onset of hyporeactivity, 5 to 6 days without each inducer were required before normal serum interferon levels could be stimulated. Animals also developed a hyporeactive state as a consequence of Semliki Forest or encephalomyocarditis virus infections. By day 2 of either infection, mice had a suppressed interferon response to tilorone HCl, but remains responsive to poly(I:C) or U-25,166 until day 4. In vivo, poly(I:C) stimulated interferon production in a variety of cells and organs, whereas the tilorone HCl and U-25,166 responses involved a nonlymphoid component of the reticuloendothelial system. In vitro, poly(I:C) induced interferon in a variety of murine cells, U-25,166 was active in murine thymus and spleen organ cultures, and tilorone was inactive. These data indicate that U-25,166 is an interesting low-molecular-weight interferon inducer.
D000818:Animals; D000998:Antiviral Agents; D005260:Female; D005449:Fluorenes / Q000494:pharmacology*; D007369:Interferon Inducers / Q000494:pharmacology; D007372:Interferons / Q000032:analysis; D051379:Mice; D011070:Poly I-C / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects; D013994:Tilorone / Q000494:pharmacology*; D014777:Virus Diseases / Q000188:drug therapy
D000998:Antiviral Agents; D005449:Fluorenes; D007369:Interferon Inducers; D011743:Pyrimidines; D007372:Interferons; D013994:Tilorone; D011070:Poly I-C