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The antiviral effect of 3 derivatives of benzo(c)fluorenone against encephalomyocarditis (EMC) and vaccinia viruses in mice was compared with that of tilorone hydrochloride (THCl). All 3 derivatives were effective against either virus following single-dose oral application as well as after 4-times repeated subcutaneous (s.c.) treatment, but following oral administration only the VUFB 14162 derivative exerted an antiviral effect corresponding to that of THCl. After s.c. application, however, VUFB 14162 derivative was less toxic than THCl. Two benzo(c)fluorenone derivatives, namely VUFB 14162 and 13431, induced in mouse sera the levels of interferon (IFN), which production kinetics and hyporeactivity phenomenon were comparable with those induced by THCl. Because no IFN was found following administration of the third VUFB 13371 derivative, its antiviral effect consisted probably in an other than IFN-inducing mechanism.

Like tilorone . HCl, its analogues, bis-pyrrolidinoacetamido-fluorenone (MLU-B75), and bis-dipropylaminoacetamido-fluorenone (MLU-B76), significantly protected mice against intraperitoneal challenge with a lethal dose of Mengo virus when administered prophylactically in a single oral dose of 250 mg per kg body weight. At lower doses the antiviral activity of MLU-B75 and MLU-B76 decreased more rapidly than that of tilorone. HCl. At the dose of 250 mg per kg the degree of antiviral protection and the titre of interferon induced by tilorone. HCl correlated well, but there was no correlation between the extent of protection and the detected amount of virus inhibitor induced by MLU-B76. It remains to be determined whether the antiviral protection elicited by the analogues of tilorone is mediated by interferon.