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I TAMM

Publications and source records attributed to I TAMM.

At least 73 records · Page 4Linked to original sources
PubMed1954

Inhibition of influenza virus multiplication by N-glycosides of benzimidazoles-N.

Chloro derivatives of benzimidazole were found to be 2 to 3 times more active than corresponding methyl derivatives in causing inhibition of Lee virus multiplication in chorioallantoic membrane cultures in vitro. The most active benzimidazole derivative thus far tested is 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB); it caused 75 per cent inhibition of Lee virus multiplication in membrane cultures at a concentration of 0.38 x 10(-4)M. On the other hand, 5,6-dimethyl-1-alpha;-D-ribofuranosylbenzimidazole, the moiety present in vitamin B(12), failed to inhibit Lee virus multiplication at a concentration of 35 x 10(-4)M. Other N-glycosides of 5,6-dichlorobenzimidazole were considerably less active than DRB. In single cycle experiments, the degree of inhibition of Lee virus multiplication by DRB in membrane cultures was not dependent on the amount of virus in the inoculum. This compound did not inactivate the infectivity of extracellular Lee virus, had no effect on virus-erythrocyte interaction, did not interfere with the adsorption of the virus by the host tissue, nor affect the release of newly formed virus from the membrane. The inhibitory effect of DRB on Lee virus multiplication, in contrast to that of 2,5-dimethylbenzimidazole, persisted after transfer of infected membranes into fresh culture medium not containing the compound. Both DRB and the 2,5-dimethyl compound caused 99 per cent inhibition of Lee virus multiplication without affecting oxygen uptake of the membrane. Tissue proliferation of membrane pieces in roller tube culture was not significantly affected by DRB at inhibitory concentration, whereas at equivalent concentration the 2,5-dimethyl compound did restrict cellular growth. At higher concentrations, both compounds caused retardation of cell proliferation. This effect was reversible on removal of either compound from the medium. The multiplication of several strains of influenza A and B viruses, i.e. Lee, MB, PR8, and FM1, was inhibited to the same degree by each of the two compounds; DRB was 35 times more active than the 2,5-dimethyl compound relative to each of the strains. DRB caused inhibition of Lee virus multiplication in intact embryonated chicken eggs and in mice without causing significant signs of toxicity in either host. Some of the implications of these findings are discussed in relation to the mechanism of the inhibition of influenza virus multiplication.

Animals↗
PubMed1953

Inhibition of influenza virus multiplication by alkyl derivatives of benzimidazole. I. Kinetic aspects of inhibition by 2,5-dimethylbenzimidazole as measured by infectivity titrations.

At a concentration of 0.0026 M, 2,5-dimethylbenzimidazole caused a number of alterations in the first cycle of multiplication of influenza B virus, Lee strain, in chorioallantoic membrane cultures in vitro. As determined by infectivity titrations in ovo on the membrane per se, the following alterations were observed: The duration of the latent period was increased by 80 per cent. The rate of increase in titer during the incremental period was somewhat decreased. The yield of virus was decreased by about 99 per cent. When the compound was added to membrane cultures at various periods before or after inoculation with the virus, the following findings were obtained: On addition before or along with the virus, the substance caused about 99 per cent inhibition of multiplication. When added during the first 2 hours after inoculation, the compound caused inhibition of a degree which was inversely proportional to the time of addition. When added 3 to 8 hours after inoculation, the substance caused about 80 per cent inhibition. When added after the end of the latent period, no definite inhibition was obtained in the first cycle of multiplication. These results are interpreted as indicating that 2,5-dimethylbenzimidazole acts by reducing the rate of biosynthetic mechanisms necessary for the reproduction of influenza virus particles.

Benzimidazoles↗
PubMed1953

Inhibition of influenza virus multiplication by alkyl derivatives of benzimidazole. II. Measurement of inhibitory activity by hemagglutination titrations.

The activity of compounds which inhibit the multiplication of influenza virus can be measured in chorioallantoic membrane cultures in vitro by means of hemagglutination titrations on the medium. Studies on the reproducibility of virus reproduction in membrane cultures have revealed the major variables which affect the results and thus have led to the development of a precise technique. Under strictly controlled experimental conditions, the extent of reproduction of the virus in membrane cultures is predictable within narrow limits of variation. With 10(5.5) EID(50) of influenza B virus, Lee strain, and 5.75 cm.(2) of chorioallantoic membrane per ml., the ratio of infective virus particles to susceptible allantoic cells appears to be approximately 1:28. Under these conditions, the evidence indicates that two cycles of multiplication occur and nearly maximal hemagglutination titers are found with culture medium at 36 hours. The extent of the deviation in the absolute titer in different experiments was only 0.112 log unit. At a concentration of 0.0017 M, 2,5-dimethylbenzimidazole caused inhibition of the multiplication of influenza B virus, Lee strain, which persisted for at least 70 hours as measured by hemagglutination titrations on the culture medium. The degree of inhibition was closely comparable to that demonstrated by infectivity titrations on the membrane at the end of the first cycle of virus reproduction (1).

Benzimidazoles↗
PubMed1953

Inhibition of influenza virus multiplication by alkyl derivatives of benzimidazole. III. Relationship between inhibitory activity and chemical structure.

The degree of inhibition of multiplication of influenza B virus, Lee strain, in membrane cultures in vitro appears to be directly related to the concentration of the inhibitory compounds used in this investigation. With each of the alkyl derivatives of benzimidazole, evidence for such a relationship was obtained in the range between 60 and 90 per cent inhibition of virus multiplication. Alteration of the structure of benzimidazole by substitution of alkyl radicals at various positions in either the benzene or the imidazole ring resulted in diverse differences in the capacity to inhibit influenza virus multiplication in vitro. Minor increases in inhibitory activity resulted when one to three methyl groups were introduced at certain positions in the molecule. Marked increases in inhibitory activity were achieved by more extensive substitution in either the benzene or the imidazole ring. The position and nature of substituent groups appeared to be of decisive importance. Among the more highly active compounds were 2,4,5,6,7-pentamethyl-benzimidazole, 5,6-diethylbenzimidazole, and 2-ethyl-5-methylbenzimidazole. Further extension of the alkyl chain at position 2 caused no significant change in the inhibitory activity of the derivative. The most active compounds studied caused 75 per cent inhibition of Lee virus multiplication in membrane cultures in vitro at concentrations of approximately 0.0002 M. Some of the implications of these findings are discussed.

Benzimidazoles↗
PubMed1952

A mucoprotein derived from human urine which reacts with influenza, mumps, and Newcastle disease viruses.

A mucoprotein, present in normal human urine, has been isolated and obtained in a state of a high degree of purity. A number of the biological, chemical, and physicochemical properties of the substance have been studied. From the results obtained in the present investigation and those reported in succeeding papers (34, 35) it appears that the mucoprotein has a high molecular weight, i.e., of the order of 7.0 x 10(6), consists of thread-like molecules which have axial ratios of approximately 100, and is specifically antigenic. This substance, which appears to be free of contaminating material, possesses in extraordinary degree the capacity to react with influenza, mumps, and Newcastle disease viruses. At equilibrium, with influenza virus, the minimal amount of the substance capable of giving a demonstrable reaction with one hemagglutinating unit of virus appears to be about 0.0003 microg. The mucoprotein is altered by preparations of influenza viruses and its capacity to react with these agents or others is lost. The kinetics of the inactivation process brought about by influenza viruses is in accord with those of well known enzyme-substrate systems. With the exception of the capacity to react with viruses, altered mucoprotein did not differ from the native substance relative to any of the properties examined in the present study. That certain physicochemical properties of the altered mucoprotein are different from those of the native substance is demonstrated in succeeding papers (34, 35).

Animals↗