Tilorone Hydrochloride: Mode of Action

Mayer, Gerald D.; Krueger, R F

doi:10.1126/science.169.3951.1214

Cited by 136 publications

(83 citation statements)

References 2 publications

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“…It has also been shown to be effective against intranasal infection by vesicular stomatis virus (VSV; 2). Its mode of action is presumably interferon stimulation (2,6). We have investigated the protection elicited by different doses of tilorone given intraperitoneally against MM virus infection in mice.…”

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confidence: 99%

Tilorone Hydrochloride: Lack of Correlation Between Interferon Induction and Viral Protection

Giron¹,

Schmidt²,

Pindak³

1972

Antimicrob Agents Chemother

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The protection of mice against MM virus infection and the induction of circulating interferon by tilorone hydrochloride were determined. Whereas protection was evident with doses of 0.15 and 1.5 mg/kg, interferon was not detected with doses lower than 150 mg/kg. Protection was apparently not dependent on interferon induction.Tilorone hydrochloride, the orange, watersoluble dihydrochloride salt of 2,7-bis[2-(diethylamino) ethoxy] fluoren-9-one, is a broadspectrum antiviral agent (5). In mice, it is effective against Semliki Forest virus by the oral, subcutaneous, and intraperitoneal treatment routes. It has also been shown to be effective against intranasal infection by vesicular stomatis virus (VSV; 2). Its mode of action is presumably interferon stimulation (2, 6). We have investigated the protection elicited by different doses of tilorone given intraperitoneally against MM virus infection in mice. At the same time, the amount of circulating interferon induced by each dose of tilorone was determined.Female Swiss Webster mice weighing about 14 g were treated intraperitoneally with different doses of tilorone diluted in Hanks balanced salt solution. Ten mice from each group were bled at 6, 12, and 24 hr after the administration of tilorone. The blood was pooled, and the plasma was collected and assayed for interferon activity. At 24 hr after the injection of tilorone, the mice remaining in each group were challenged intraperitoneatly with about 100 plaque-forming units of MM virus (2 LD50). Deaths were recorded daily for 20 days. The results (Table 1) show that, in terms of mortality and mean survival time, a tilorone dose of 7.5 mg/kg was sufficient to protect mice. They also suggest that doses as low as 0.15 and 1.5 mg/kg can have a protective effect, although at these doses the results were variable. Circulating interferon, however, was not detected with tilorone doses of less than 150 mg/kg. As these data show, in our system there was no correlation between the protection of mice against MM virus infection and the amount of circulating interferon induced by tilorone.These results are not in agreement with those of De Clercq and Merigan (2), who reported that the degree of protection of mice against intranasal infection with VSV was directly related to the titers of interferon induced by different doses of tilorone. Their interferon titers in response to tilorone were much higher than those in the present study. Since the 50% reduction in plaque count as a method for assay of interferon is more sensitive when MM virus is the challenge agent than when VSV is used (1), we must conclude that the differences in interferon titers in the two studies are real. This discrepancy could be due to a genotypic difference in the animals.

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confidence: 99%

Tilorone Hydrochloride: Lack of Correlation Between Interferon Induction and Viral Protection

Giron¹,

Schmidt²,

Pindak³

1972

Antimicrob Agents Chemother

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“…Mayer and coworkers [5,61 have identified this compound as an interferon inducer and established a relationship with the antiviral activity. However, recently a lack of correlation between interferon induction and viral protection by tilorone hydrochloride has been reported…”

Section: Introductionmentioning

confidence: 99%

Mode of tilorone hydrochloride interaction to DNA and polydeoxyribonucleotides

Prakash

Zunino²,

Gaur

et al. 1972

FEBS Letters

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“…The inducers studied most frequently are large anionic polymers (6,25), highly base-paired ribonucleic acids (5,9), and polycarboxylates (4,8), which are difficult to characterize because of their polydispersity and because they caused toxic side effects (2,7,16,19). Some low-molecular-weight inducers, such as tilorone hydrochloride (18), quinacrine (10), BL-20803 (24), CP-20961 (12), and cycloheximide (30), were also examined for their antiviral effects, with unencouraging results. Tilorone hydrochloride (18), an orally active inducer in mice, and CP-20961, which has a high therapeutic index (300) in the infection model of vesicular stomatitis virus, showed little, if any, protective activity against influenza virus infection in mice (12).…”

mentioning

confidence: 99%

Antiviral and Interferon-Inducing Activity of a New Glutarimide Antibiotic, 9-Methylstreptimidone

Saito

Suzuki

Sasaki

et al. 1976

Antimicrob Agents Chemother

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The antiviral effect of 9-methylstreptimidone (9-MS) was examined in mice infected with mouse-adapted influenza A2 (H2N2) virus. Both a single and continuous prophylactic administration of 9-MS protected mice from virus infection, and comparison between the minimal effective and the 50% lethal dose gave a therapeutic index of 60. When the treatment was started after infection, however, no antiviral effect was demonstrated. After a single intraperitoneal administration of 9-MS, a highly potent virus-inhibitory factor was detected in the lungs (10 h later) and the sera (16 h later) of uninfected mice, which was assumed to be an interferon on the basis of the biological characteristics. These results suggest that the protective activity of the antibiotic is due to interferon induction in mice.

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Tilorone Hydrochloride: Mode of Action

Abstract: An antiviral serum component is found in mice treated orally with tilorone hydrochloride. The active material fulfills sufficient biological criteria to be classified as an interferon.

Cited by 136 publications

References 2 publications

Tilorone Hydrochloride: Lack of Correlation Between Interferon Induction and Viral Protection

Tilorone Hydrochloride: Lack of Correlation Between Interferon Induction and Viral Protection

Mode of tilorone hydrochloride interaction to DNA and polydeoxyribonucleotides

Antiviral and Interferon-Inducing Activity of a New Glutarimide Antibiotic, 9-Methylstreptimidone

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