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PubMed1985

Derivatives of benzo(c)fluorene. VI. Antiviral and interferon-inducing activities of three benzo(c)fluorenone derivatives in mice.

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.

Animals↗
PubMed1987

Derivatives of benzo(c)fluorene. XXIV. Cytostatic effect of benfluron on human leukemic cells in vitro.

Benfluoron (BF), a new cytostatic drug, synthesized at the Institute of Pharmacy and Biochemistry in Prague, was tested for its cytostatic and cytotoxic effect. The concentrations of BF ranging from 0.1-2 micrograms/ml had a significant cytostatic effect on nine stabilized human leukemic cell lines. This effect was demonstrated by cell counts, cell viability and 3H-thymidine incorporation. The BF concentrations of 2 micrograms/ml and higher were considerably cytostatic causing the cell death and cell degradation. The effect of BF on the cell growth being irreversible could not be eliminated by washing the cells and recultivating them in fresh medium. The BF concentrations halving the total number of viable cells (EC50 value) induced a higher cytotoxicity in lymphoblastoid cell lines then in myeloid ones. BF did not influence the binding of monoclonal antibodies with membrane markers of different cell subpopulations. Prospective application of BF as a cytostatic and immunosuppressive drug is discussed.

Antibodies, Monoclonal↗
PubMedDate not supplied

Depression of the hepatic cytochrome P-450 mono-oxygenase system by administered tilorone (2,7-bis(2-(diethylamino)ethoxy)fluoren-9-one dihydrochloride).

The oral administration of the antiviral agent, tilorone-HCl (50 mg/day for 4 days) to rats caused losses of hepatic microsomal ethylmorphine N-demethylase, benzo(a)pyrene hydroxylase and aniline hydroxylase activities of 50, 44 and 22%, respectively. Microsomal levels of cytochrome P-450 and NADPH-cytochrome c reductase were lowered by 40 and 20% respectively, but levels of cytochrome b5 and NADH-cytochrome c reductase remained unchanged. After a single oral dose of tilorone-HCl (50 mg/kg) a loss of 38% of the microsomal cytochrome P-450 and 25% of the ethylmorphine N-demethylase activity was observed within 24 hr; recovery was complete within 8 to 10 days. Hexobarbital sleeping times and blood levels were elevated after tilorone administration (20 or 50 mg/kg/day for 4 days). In vitro, tilorone-HCl showed no inhibitory effect on microsomal drug metabolism nod did it affect the cytochrome P-450 content of the microsomes. The rate of incorporation of delta-amino(3H)levulinic acid into cytochrome P-450 was not affected by tilorone-HCl.

Aniline Hydroxylase↗
PubMed1983

Fluorene.

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Animals↗