Antiviral Activity of BL-3849A, a Low-Molecular-Weight Oral Interferon Inducer

Abstract

Oral administration of BL-3849A to adult mice resulted in peak serum interferon titers of 4,000 units from 15 to 30 h after administration, with detectable levels persisting until 48 h. After intraperitoneal (i.p.) inoculation, peak serum interferon titers of 1,000 to 3,000 units were noted between 9 and 18 h. Multiple injections of the inducer by either route resulted in a marked decrease in the interferon response with each successive dose. In mice infected intranasally with the Rochester mouse virus strain of encephalomyocarditis virus, oral treatment with BL-3849A reduced mortality when initiated either 18 h before or 1 h after infection. In contrast, administration of drug by the i.p. route decreased mortality only if begun before infection. In mice inoculated i.p. with encephalomyocarditis virus, treatment by both the oral and the i.p. route decreased the mortality whether initiated 18 h before or 1 h after infection. Treatment by the oral, but not the i.p., route reduced mortality of mice inoculated i.p. with Semliki forest virus or Herpesvirus hominis type 2. BL-3849A appeared to be as effective as tilorone hydrochloride, but less effective than polyriboinosinic-polyribocytidylic acid, in the treatment of these viral infections of mice.

1H-Pyrazolo[3,4-b]quinolines: Synthesis and Properties over 100 Years of Research

“…The results show that some of the derivatives also showed high interferon-inducing activity. One of the derivatives, 4-[(3-(dimethyloamino)propyloamino] -1,3,7-trimethyl-1H-pyrazolo [3,4-b]quinoline hydrochloride (Figure 19c), was also tested by Kern et al [193], and again, the compound induced high levels of circulating interferon, which effected, with significantly reduced mortality, the mice that were infected with the Rochester mouse virus, Herpesvirus hominis, Semliki forest virus and the vesicular stomatitis virus. The authors also observed the strong hyporeactivity of the interferon after multiple doses of 4-[(3-(dimethyloamino)propyloamino]-1,3,7-trimethyl-1H-pyrazolo [3,4-b] quinoline hydrochloride.…”

Stimuler la réponse interféron de type I avec des petites molécules : le renouveau d’une vieille idée

“…Par la suite, plusieurs composés hétérocycliques inducteurs des interférons de type I sont isolés, notamment le CMA (10-carboxyméthyl-9-acridanone) et différents dérivés de l'acridine (Acranil r , mépacrine) (Glaz et al, 1973 ;Taylor et al, 1980b ;Kramer et al, 1981), des 1,5diamino anthraquinones (Stringfellow et al, 1979), des quinolines comme le BL-20803 (Siminoff et al, 1973), des dérivés des pyrimidines comme la bropirimine (Stringfellow et al, 1980), des dérivés diaminés tels que le CP-20,961 (Hoffman et al, 1973), et enfin l'acide flavone acétique (Hornung et al, 1988). Plusieurs de ces molécules présentent une puissante activité antivirale chez la souris en corrélation avec leur capacité à induire les interférons de type I Hoffman et al, 1973 ;Kern et al, 1976 ;Kramer et al, 1976 ;Stringfellow et al, 1979 ;Taylor et al, 1980a), mais les tests réalisés chez l'homme ont été très décevants sans que l'on en comprenne véritablement les raisons (Kaufman et al, 1971). À la fin des années 80, les travaux sur ces composés se marginalisent, sauf en Russie où le tilorone hydrochloride et le CMA sont toujours prescrits comme antiviraux (Silin et al, 2009).…”

Antiviral Activity of Extracts from Marine Algae

“…In addition, we evaluated the efficacy of these substances in mice inoculated with encephalomyocarditis virus (EMCV), Semliki Forest virus (SFV), or murine cytomegalovirus (MCMV). MATERIALS (3,(7)(8)(9)(10) Cell cultures and media. Fetal lamb kidney cells were used for HSV titrations, and mouse embryo fibroblast (MEF) cells were used for in vitro virus susceptibility assays.…”